Supplementing Manganese might unblock the Urea Cycle?

[triffid113]

Huh. I find that high ammonia can also disturb the Kreb/TCA cycle and lower energy. Another way to CFS/FM symptoms: Ammonia inhibits α-ketoglutarate dehydrogenase or oxoglutarate dehydrogenase, and the depletion of carboxylic acids, which are used for glutamine synthesis, paralyzes the Krebs cycle. The production of adenosine 5′-triphosphate and nicotinamide adenine dinucleotide (reduced form) in the Krebs cycle is decreased, and pyruvate conversion to lactate is increased [17]. [Lactate is the output of the Krebs cycle when it cannot fully break down your food and instead ferments it resulting in only 2 ATP (unit of energy) vs. 50-some ATP (if the Kreb cycle has proper nutrition and absence of ammonia!) to run].

Here is the reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852716/

This paper also states that: l-Carnitine, a metabolic product of amino acids, activates UC enzymes and increases the elimination of free radicals by participating in the transportation of short-chain fatty acids through the peroxisomal and mitochondrial membranes [47]. A treatment with l-carnitine significantly reduced blood ammonia and improved patient mental status [48,87].

And

The sugar lactulose has been shown to reduce the production of ammonia by the gut bacteria, as well as promote the excretion of ammonia through the feces.

Both of which might be helpful.

A table in the above paper also lists various microbiota which cause ammonia consumption in the gut...most of these are lactobacillus contained in my GI With Pahge supplement from Life Extension. It goes on to say: probiotics have a role in reducing the total amount of ammonia in the portal blood because probiotics inhibit bacterial urease activity, which may be due to lactic acid [100,101]. Probiotics also decrease intestinal permeability and bacterial urease secretion, increase ammonia excretion, and improve the nutritional status of the gut epithelium cells. As most probiotics produce acids that reduce the pH in the intestine, ammonia absorption also decreases. In addition, probiotics reduce inflammation and oxidative stress in liver cells, which leads to increased hepatic clearance of ammonia and reduced uptake of other toxins.

This is all a digression as you believe ammonia is not a problem for you. Tests cost money - I get that. Too bad.

I want to mention that expecting to be cured by one supplement is not likely. Wanting to understand is great, but it likely takes a synergy of supplements to improve most people. In my day, people took multi vitamins to ensure they got the full spectrum of necessary nutrients. Of course, now we know that unless you take a many pill multi, this cannot be done, as the needed nutrients cannot be compressed into one pill (I point to calcium, whose only compressible form is carbonate, which is only 5% absorbable, and, thus, a joke).

 

[triffid113]

Found this:
What is the relationship between the citric acid [TCA/Kreb] cycle and the urea cycle?


The urea cycle is closely linked to the citric acid cycle deriving one of its nitrogens through transamination of oxalacetate to form asparate and returns fumarate to that cycle.
. . . .
So... improving the TCA cycle might be importantt to improving the Ornithine cycle. Most often lacking are B vitamins and magnesium, required for the TCA/Kreb cycle.

 

[triffid113]

So, being male, your problem is peeing too much, especially at night? It usually is from an enlarged prostate which happens to some huge percentage (90%) of men over time. Supposedly saw palmetto helps that, over a loooong time. I believe it's a 5 alpha reductase inhibitor. Which means it keeps your testosterone from turning into DHT. Ethnobotanist Dr. James Duke, for imstance, says to take Saw Palmetto every day of your adult life if you're male. I am female but I take a supplement from Life Extension called Triple Cruciferous Vegetable (to ward off breast cancer) and one of the things in it is chrysin, which is also a 5-alpha-reductase inhibitor. idk the relative strengths of these 5AR inhibitors, but I read somewhere you can get too much 5AR. Thus, the slow and steady route is the way to go and you won't get fast results (if any, because until you try things for yourself, you never know what will help YOU). idk if this has any impact on Ornithine (douvtful) but possib ly your symptoms are not from low ornithine.

 

[triffid113]

Sorry, I got pretty interested in the new stuff I found about high ammonia...all a digression. Take care. You are a pioneer in ornithine management here. Report back when you figure it out. I said "when" with faith in both you and the fast pace of science.

 

[Violeta]

It's a blood aminoacid test, it was processed in Germany and it gave the levels of 29 aminoacids from a single blood draw. From my results, values relevant to the urea cycle are:
Arginine __________ 15.9 mg/L ______ Normal range is: 2.6 - 22.3 mg/L
Citrulline __________ 4.2 mg/L ______ Normal range is: 2.1 - 9.6 mg/L
Ornithine _________ 6.1 mg/L _______ Normal range is: 6.3 - 25.8 mg/L !!!

@cristi_b, did the blood aminoacid test measure lysine?

 

[Alvin2]

@triffid113 your posts make me think of Hepatic Encephalopathy

 

[cristi_b]

Interesting, what is this test called?

Direct translation would be "Plasma aminoacids".

@cristi_b, did the blood aminoacid test measure lysine?

Yes it did. My lysine levels, measured at 28.7 mg/L, are inside the reference range of the laboratory 17.4 - 35.5 mg/L.

So do we know if you can get high ammonia from a high protein diet, regardless of if you have the gene making it hard to excrete ammonia? (Do you eat a high protein diet?).

I eat a lot of meat products, I can't function without them. Whenever I try to reduce the meat I eat I feel very hungry, my hands feel shaky and I can't concentrate. It's like I'm addicted to it. I don't know what it is in the meat that my body needs so desperately, probably protein to make aminoacids. I have very peculiar problems.
Since first opening this topic my urea and BUN levels have went down, so I'm pretty sure ammonia has went down also, but I can't test it again since the lab I used to go to for blood tests no longer offer an ammonia test.

I don't think your lab is correct about the D level needed. Most docs/hospitals claim it is 50ng/ml but Life Extension says it is 70 and I believe them. I keep mine between 70 nj/ml-100ng/ml

I've done an additional Vitamin D test and came out at 11 ng/mL. I cannot supplement with vitamin D because my allergies go into overdrive, there have situations where I felt my throat start to close up and getting difficult to breathe, headaches, dizziness etc I simply cannot take vitamin D and now also stay away from the sun(I've stayed mostly indoors for about 9 years without realizing that the sun is the problem). In spite of my ultra low inactive vitamin D I have upper-normal active vitamin D and now I'm thinking this type of vitamin D(the active 1,2 OH2D kind) is correlated to my allergies.

So, you are male...men need more citrate and zinc in their prostate.

I have supplementing with Magnesium Citrate and Zinc as cofactors for activating Vitamin D. This was when I did not suspect that it's the active Vitamin D that is making my allergies worse(see this forum post). It does nothing for my urinary problems.

Did I read you tried P5P? I think of P5P and magnesium together...they are both required for excretion of harmful substances, including homocysteine, in the liver. So if you tried P5P and it was problematic, try that with magnesium and see if it makes a difference.

My homocysteine is normal, I have done a blood test for it. Also the P5P I tried out had Magnesium: it was a Magnesium P5P combo and nothing good came out of it, it just caused more urinary problems.

Ammonia inhibits α-ketoglutarate dehydrogenase or oxoglutarate dehydrogenase, and the depletion of carboxylic acids, which are used for glutamine synthesis, paralyzes the Krebs cycle. The production of adenosine 5′-triphosphate and nicotinamide adenine dinucleotide (reduced form) in the Krebs cycle is decreased, and pyruvate conversion to lactate is increased [17]. [Lactate is the output of the Krebs cycle when it cannot fully break down your food and instead ferments it resulting in only 2 ATP (unit of energy) vs. 50-some ATP (if the Kreb cycle has proper nutrition and absence of ammonia!) to run].

Now this is interesting because I tested out lactate in my blood and came out exactly at the upper limit 2.19 mmol/L while limit was 2.2 mmol/L, so basically if you take into account the error rate of the lab for such a test, I could very well be above the limit and on my way to develop lactic acidosis. Also NADH, the reduced form of nicotinamide adenine dinucleotide, causes urinary troubles for me. I've seen part of this information in the past(that ammonia inhibits AKG) and actually ordered an Arginine+AKG supplement, but the trouble was that it had too much Arginine and too little AKG in it and since Arginine just amplified the urinary problems I could not observe the AKG effect. I will have to buy some AKG supplement that does not have Arginine in it in order to observe if it helps with something.

l-Carnitine, [...] lactulose

I've used both l-Carnitine and Lactulose when I was trying to lower my ammonia level, I don't know how much each of these helped but I remember they used to give me a lot of gas. I think Lactulose should be taken only with a certain antibiotic, don't remember the name of it(which I presume that kills the bacteria that produces the gas).

s microbiota which cause ammonia consumption in the gut...most of these are lactobacillus contained in my GI With Pahge supplement from Life Extension. It goes on to say: probiotics have a role in reducing the total amount of ammonia in the portal blood because probiotics inhibit bacterial urease activity, which may be due to lactic acid [100,101].

Recently I've had a very bad experience with a probiotic strand called HN019, which caused severe algeries for me. I'm reluctant to try an other probiotic since these also have an effect on the immune system. I need to get a grip on my allergies before I try that again.

 

[cristi_b]

So, being male, your problem is peeing too much, especially at night?

I did not want to get into the details, because it's kind of embaracing, it's not just peeing at night, it's several types of urinary issues amplified by supplements:
1) frequent need/urge to urinate: can even be after 1h from previous urination and unable to delay it; I usually don't wet myself on the way to the bathroom because I don't try to delay
2) increased pressure when urinating even if the overall quantity is small: it's like my body thinks the urine is something bad and wants to get it out as fast as possible; you would expect for this to happen when the bladder is full of a large volume of urine, but no, this happens to me even on small quantities
3) urinary dribbling: this happens after urination, I finish or at least I feel there's no more urine, I leave the bathroom and small droplets leak and I wet myself slightly; this dribbling happens for 5-10 minutes, only after urination and without any sensation except a cold feeling from wetting my briefs; I read something about "normal pressure hydrocephalus" that would cause this or at least something similar

Supposedly saw palmetto helps that, over a loooong time. I believe it's a 5 alpha reductase inhibitor. Which means it keeps your testosterone from turning into DHT.

Maybe I'll order that as well, the trouble is I have so many supplements in my house that I've tryed for various theories, most of which I've only partially used. My room is like a pharmacy. I keep telling myself that complicated problems take up a lot of trail and errors.

idk if this has any impact on Ornithine (douvtful) but possib ly your symptoms are not from low ornithine.

Recently I've came accross 2 additional theories, besides the Ornithine thing:
1) High histamine / mast cells problem: this can also happen to the bladder
2) High Nitric Oxide which can cause detrusor overactivity

Those 2 theories might be just me being overly optimistic, as Ornithine supplement is the most dangerous for my bladder. ODC enzyme in the brain has been linked to Alzheimer and coincidently I also have some memory problems, plus lots of relatives on my father's side with dementia(including my father). It could very well be that low Ornithine is an early symptom of Alzheimer's. My father reacts the same as me to these supplements and he has, as I said, an Alzheimer's diagnosis.

 

[cristi_b]

One more theory about my low Ornithine: Aspergillus Fumigatus uses Ornithine for siderophore biosynthesis.

There are some coincidences between my condition and A. Fumigatus infection:
- high Iron: this pathogen needs iron for virulence and tries to ensure its acquisition
- low Ornithine: used by the microbe to produce siderophores
- spent a lot of time as a kid near Tulips: these flowers are known as a vector for A. Fumigatus
- spots/shadows on my lungs and difficulty breathing when I was a kid: this is the place of infection
- vitamin D problems: A. Fumigatus can induce local production of active vitamin D because of inflammation
- histamine problems: inflammation leads to a lot of histamine release and makes any issue like MCAS worse

In the next period I will test for this and let you know the results.