Anxiety, Ammonia, and the NMDA Receptor

[Lotus97]

Oh no, I just ordered some Ornithine Alpha Ketoglutarte, Tyrosine AKG, and Creatine AKG in hopes of detoxing ammonia from my high protein diet.

I eat a lot of meat so I'm probably getting enough aspartic acid although I'm not sure how efficient my body is able to utilize amino acids from foods. I was taking ZMA to improve my quality of sleep and then switched to taking Zinc/Mag Aspartate separately to save money. I was taking ZMA before bed and it didn't seem to affect my sleep negatively. I also just ordered Lithium Aspartate because that was on sale and a lot cheaper than Lithium Orotate.

Speaking of Lithium, has anyone tried that for anxiety? There might be some risks with that though so it might something to take as needed rather than every day.

 

[Gestalt]

Speaking of Lithium, has anyone tried that for anxiety? There might be some risks with that though so it might something to take as needed rather than every day.

I take Lithium Orotate. Can't say I have noticed any difference. I know that for some people it works wonders though.

 

[adreno]

Could akg and/or aspartic acid be beneficial for anxiety & Ammonia issues? I remain confused.

Yes, it looks like they will help with ammonia, but might increase neurostimulation by themselves. I think there are no easy answers. It is probably all about balance. We have to remember that excitatory neurotransmitters are not bad, and are needed just as much as the inhibitory ones. But we need to achieve balance, which is not easy (I am working on this myself).

I haven't felt much from lithium aspartate, but the orotate version has a very pronounced calming effect. I believe it might cross the BBB better.

 

[Hip]

I have found any supplement that contains arginine seems to reduce my anxiety. This includes L-arginine powder (at a dose of a few heaped teaspoons) and arginine pyroglutamate powder (which crosses the blood-brain barrier very well, so you will find only one heaped teaspoon is required). I have also tried arginine alpha ketoglutarate, and ornithine alpha ketoglutarate, and these work too.

It takes an hour or two for the anti-anxiety effects of oral arginine to kick in, I find. But long term arginine use tends to cause a herpes cold sore flare ups in me, so I am always concerned about taking arginine regularly, in case it generally boosts herpes infections in the body.

I am not sure what the anti-anxiety mechanism of arginine might be. Certainly arginine removes ammonia, so if ammonia-driven NMDA receptor stimulation was the cause of your anxiety symptoms, then this could explain why arginine has anti-anxiety effects.


Intranasal L-Arginine — A New Technique

One particularly useful trick that I recently figured out is taking small doses of L-arginine powder intranasally: that is to say, snorting around 50 mg of L-arginine powder into each nostril with a drinking straw.

Not only does intranasal arginine have very powerful effects against anxiety symptoms, but moreover, its anti-anxiety effects kick in fast: we are talking about 20 minutes. You can be feeling quite high levels of anxiety, yet just 20 minutes later, after snorting a small amount of arginine, you are calm again. I don't know any other supplement that is this fast acting. So intranasal arginine is very good for those anxiety emergencies, when your anxiety levels have hit a high, and you want to regain a calm state quickly.

Also, since your overall intranasal arginine dose is much smaller than the oral heaped teaspoon dose required to achieve the same anti-anxiety effects, snorting is probably less likely to cause herpes flare ups.

Of course, proceed at your own risk. Intranasal arginine is an experimental treatment, and I am not sure if some adverse effects might arise from taking arginine intranasally. Though I have not had any problems in all the times I have snorted L-arginine powder.

Note: do not snort any supplement into your nose that is acidic (ie, tastes tart), as it will sting like hell.

 

[Hip]

I think that L-cartitine, at around 1500 mg daily, is another good approach if you think ammonia may be causing your anxiety symptoms. L-carnitine suppresses the neurotoxicity of ammonia. Ref: here. Plus L-carnitine is a useful energy booster for ME/CFS.

 

[Lotus97]

I find Arginine/Citrulline/Ornithine too stimulating at higher doses, but a lot of things people take for anxiety can have the opposite effect on others. I also take L-Carnitine Fumarate which is also too stimulating at higher doses so I only take 1/3 a capsule at a time. At that dose it's a little bit physically stimulating, but mentally relaxing and also boosts my mood. Although I'm sure there's some synergy between my other supplements and prescription meds if I dose carnitine right I sometimes feel like I'm stoned The dosage is a little confusing with L-Carnitine because L-Carnitine Fumarate is an 855 mg capsule of which 500 mg are L-Carnitine while L-Carnitine Tartrate just lists the dosage of a capsule as 500 mg. Fumarate is a lot more expensive, but I find it works better for me and since I take such a low dose it's not that expensive. Someone said that Tartaric acid is an antagonist to malic acid, but it's sort of theoretical whether it would make a significant difference. I noticed Purebulk.com has Carnitine powder really cheap, but it doesn't say what kind. It wouldn't be Fumarate since that's patented. Whatever it is I have no idea how it compares to Fumarate though, but I'll probably just add Acetyl L Carnitine if I want to up my dosage since that's pretty cheap in powder too and it's supposed to be better than L-Carnitine in certain regards. Oh, and no one try snorting Carnitine because that's very acidic

 

[Lotus97]

Someone posted this in another thread about methylation

Methylation itself can create glutamate directly by metabolism of histidine into a one off version of glutamate by virtue of THF in the folate cycle and I would tender that is more of a problem than people on these boards recognize when it comes to potential over-methylation.

 

[Lotus97]

I read recently that NAC can convert glutamate into glutamine. Anyone with mercury toxicity should be careful with NAC, but for most people it shouldn't cause any side effects. I also came across a post by Rich talking about how he recommends folinic acid for his methylation protocol because it helps with glutamate (although too much folinic acid could cause overmethylation). I included the second paragraph because he talks about overdriving the methylation cycle which can cause excitoxicity.
From Rich:
I actually prefer including both folinic acid and 5-MTHF. 5-MTHF is the form needed by methionine synthase, which is the enzyme with the partial block. Many people's cells are able to convert folinic acid to 5-MTHF well, but many others have inherited genetic polymorphisms that slow this conversion down considerably. The polymorphisms in the MTHFR enzyme are a good example, and these are very prevalent in the population.
Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.

I prefer hydroxocobalamin for several reasons. One is that it allows the cells to control the amounts of the coenzyme forms of B12 (methylcobalamin and adenosylcobalamin) that they make, so that they can be matched to the need. Taking methylcobalamin in large dosages by injection or sublingually can overdrive the methylation cycle, as evidenced by a major rise in sarcosine, which I've seen in amino acids testing on some people who have been on this treatment for a while. I am not comfortable with overdriving the methylation cycle, both because I think it slows flow down the transsulfuration pathway and thus limits the normalization of the balance of the sulfur metabolism, including cysteine, glutathione, taurine and sulfate, and also because I am concerned about the possibility of overmethylation of DNA, which could have other deleterious effects.

 

[sregan]

Just wanted to report that, I started taking Yucca (500mg) about an hour after each meal, and it has made a remarkable difference. I have much less anxiety and muscle tension in my upper back and neck has diminished considerably.


Also Apple Pectin for me seems to really boost mental clarity and helps eliminate brain fog. The fact it detoxifies Aluminum has a wonderful effects in helping eliminate ammonia. DHPR enzyme responsible for the creation of BH4 from BH2, BH4 also binds to ammonia to help eliminate it from the body. DHPR is inhibited by aluminum.

How long did the Yucca start to work for you? Was is immediate on the first pill?

 

[Gestalt]

How long did the Yucca start to work for you? Was is immediate on the first pill?

I only take 1 pill right before bedtime now. And I felt the effect after my first night taking it. So about 8 hours. Seems there are some detox process that take place at night that produce tremendous amounts of ammonia.

 

[Christopher]

I've been reading into yucca a bit for ammonia-binding and came across info. that is contains steroidal saponins. Wonder if that is having an effect as well.

 

[Lotus97]

Can yucca cause any side effects? I'm taking so many supplements and have a lot of health issues that it's hard to tell what's causing what. I think I experienced a similar side effect from a supplement that had plant sterols so I thought they were affecting my hormones because I read something about both supplements.

 

[xjhuez]

If I'm reading these two studies right, they would seem to indicate that BCAAs might help with ammonia and excitotoxicity. Of course rats ≠ humans. It also struck me as counter-intuitive (aminos should increase ammonia)

Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats

Excitatory and inhibitory amino acid neurotransmitters and ammonia metabolism in hepatic failure rats

I'm going to start on yucca at night. Are you guys taking the capsules or the liquid extract?

 

[Lotus97]

Thanks to sregan for pointing this out about pregnenolone. Too much GABA is definitely not my problem
Pregnenolone modulates two key nerve receptors in the brain, the NMDA receptors and the GABA receptors. It enhances NMDA receptor function which is involved in alertness, memory, and learning functions.

It also inhibits GABA receptors responsible for relaxation, mental slowing, sedation, and sleep. Therefore too little NMDA response combined with too much GABA action promotes mental sluggishness and depression. Conversely, by raising NMDA activity and lowering excessive GABA activity, pregnenolone acts as a natural antidepressant.

 

[triffid113]

We need DrD's take on this...he is well read on aspartate. idk - if it's related to asporotate?? My body does not like cal mag in the asporotate form. I take citrate form because the citrate inhibits/prevents kidney stones. I feel in some subtle way that this is the form of cal-mag my body likes best. That supposedly superior hexyapatate?? form of calcium does nothing for me either. I think the main thing we need to do for the ornithine cycle is take magnesium in ANY form (except oxide) because most Americans do not eat the 7-10 fruits and veggies recommended by the FDA food pyramid for health and veggies are the main source of minerals in today's diet. Most Americans eat 2 or less veggies / day.

 

[triffid113]

If I'm reading these two studies right, they would seem to indicate that BCAAs might help with ammonia and excitotoxicity. Of course rats ≠ humans. It also struck me as counter-intuitive (aminos should increase ammonia)

Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats

Excitatory and inhibitory amino acid neurotransmitters and ammonia metabolism in hepatic failure rats

I'm going to start on yucca at night. Are you guys taking the capsules or the liquid extract?

-
xjhuez, intriguing studies...and I tend to be a tad low in BCAA's. However I have NO xciteotoxicity due to taking DHEA -> estrogen and estrogen protects the NMDA receptors from excitotoxicity. So I would never know if it did the job unless I stopped DHEA and hormone replacement (I cannot it is a pellet) and ate at a restaurant with high msg (a TRULY TERRIFYING test). But it could not hurt to boost my BCAA's a little and just trust it's good for me.

 

[xjhuez]

-
xjhuez, intriguing studies...and I tend to be a tad low in BCAA's. However I have NO xciteotoxicity due to taking DHEA -> estrogen and estrogen protects the NMDA receptors from excitotoxicity. So I would never know if it did the job unless I stopped DHEA and hormone replacement (I cannot it is a pellet) and ate at a restaurant with high msg (a TRULY TERRIFYING test). But it could not hurt to boost my BCAA's a little and just trust it's good for me.

Years ago, when I first started to wonder if part of my problem was related to MSG, I bought a cheap bottle of it from a spice place and put it in a capsule. I told my wife to randomly put it in my nightly vitamins without telling me to see if it actually was the problem. Of course I knew within two hours of popping the pills, and greatly regretted completely filling the capsule. I also have the same type of reaction from supplements containing aspartate.

I've begun reducing gut ammonia with yucca, but the thing I don't understand is "cerebral ammonia metabolism".. How does the brain metabolize ammonia? This study and this study seem to indicate that too much ammonia can get into the brain if you have increased permeability or "leaky" BBB.

 

[Valentijn]

Years ago, when I first started to wonder if part of my problem was related to MSG, I bought a cheap bottle of it from a spice place and put it in a capsule. I told my wife to randomly put it in my nightly vitamins without telling me to see if it actually was the problem. Of course I knew within two hours of popping the pills, and greatly regretted completely filling the capsule.

Hell, that's hard core What did that big of a dose do to you?

 

[xjhuez]

Hell, that's hard core What did that big of a dose do to you?

Nausea, stiffness in my neck/traps, extreme thirst, some nerve tingling and what I would call flashing lights behind my eyes when I shut them. I didn't sleep a wink and had to call in sick to work.

 

[adreno]

In Asia, when you order a noodle soup, they usually dump a tablespoon of MSG in the bowl.