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Hyperammonemia & why L-Ornithine/L-Aspartate together!
jessesmom1987 Views: 18,551
Published: 12 years ago
This is a reply to # 1,371,095

Hyperammonemia & why L-Ornithine/L-Aspartate together!

Piecing together information I'm learning about ammonia and how it bypasses the liver to go to the brain.
We've all seen it in different places, about parasites/ammonia:

>>> eating the hostís cells directly or draining the best of the nutrients directly from the hostís tissues, all while secreting their faecal wastes throughout the hostís body, leaving their poisonous toxic sludge (like ammonia) behind, further taxing the host systemís abilities even more gravely. parasites likely infect everyone.
>>>When there is decreased blood flow through the liver, there can be increased levels of ammonia in the blood.

From my own experience.. parasites plug up the liver!

Detox pathways and neurotoxins:

From Cutler:

>>Liver problems are the typical cause of elevated ammonia, which does
lead to encephalopathy>>>


Portosystemic encephalopathy:

>>Absence of the detoxification function in the liver is to be regarded as the cause of PSE. This may occur as the result of an acute liver failure or a chronic liver disorder (such as adiposis hepatica, cirrhosis of the liver, portocaval shunt). Due to the partial bypassing of the blood at the liver (collateral vessels, therapeutic shunt) a reduced first-pass clearance of the liver occurs. In this way, potentially toxic substances such as ammonia or mercaptans (which are created in the lumen of the bowels by the action of bacteria on foodstuff constituents and are normally removed or detoxified during passage through the liver) get into the systemic circulation.>>>

***Due to the partial bypassing of the blood at the liver (collateral vessels, therapeutic shunt) a reduced first-pass clearance of the liver occurs***


The widely accepted hypothesis is that encephalopathy is due to a failure of hepatic clearance of gut-derived toxins. Although the exact toxins involved remain controversial, ammonia remains the toxin of interest. This has led to many investigative and therapeutic efforts aimed at identifying and eliminating the putative toxins that originate from the gut lumen

The proposed gut-derived toxins responsible for portosystemic encephalopathy include ammonia, phenols, thiols, and short-chain fatty acids. Other possible mediators include cytokines and bacterial endotoxins.

Ammonia is a neurotoxic compound that principally is eliminated from humans by its hepatic conversion to urea. Periportal hepatocytes in the liver primarily metabolize ammonia. Subsequently, urea is excreted in the urine. Residual ammonia in the hepatic sinusoidal circulation is converted to glutamine by perivenous hepatocytes expressing glutamine synthase.

several pathways may contribute to ammonia neurotoxicity. In neuropathological studies, Alzheimer type II astrocytosis is typical and likely represents the end result of these mechanisms. Astrocytes demonstrate swollen nuclei, margination of the chromatin, and a prominent nucleolus.

Astrocytes are the only cells in the brain that appear capable of glutamine synthesis (the pathway that represents the major route for cerebral ammonia detoxification).

In vivo proton MRS (1H-MRS) shows that astrocyte swelling without increases in intracerebral pressure may occur early in the pathogenesis of portosystemic encephalopathy.

Ultimately, the development of advanced portosystemic encephalopathy may be accompanied by cerebral edema, which may contribute to neurological impairment. While cerebral edema has its most obvious manifestations in the patient with fulminant hepatic failure (FHF), osmotically active substances do accumulate in the brains of patients without overt cerebral edema. An osmotically sensitive pool of myoinositol is released from astrocytes in response to osmotically induced astrocyte swelling. A depletion of myoinositol is shown by 1H-MRS in patients with chronic portosystemic encephalopathy, and it appears to correlate with an increase in the signal for glutamine and glutamate.

This didn't all come from one source, I found other things in different sources and have also added them here.


Psychoactive drug use

Valproic acid (VPA) is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia.
A more unusual but dangerous side effect of valproate is acute hyperammonemia. The mechanism by which this occurs is thought to involve valproate (VPA)-induced carnitine deficiency and inhibition of carbamyl-phosphate-synthetase, thus impairing the conversion of ammonia to urea. It has also been reported that valproate can increase the transport of glutamine across the mitochondrial membrane in the kidney, thus increasing the production of ammonia.

Vossler et al.4 described seven patients with VPA-induced encephalopathy, five of whom had elevated ammonia levels. Cerebrospinal fluid glutamine levels were also monitored and observed to be elevated in 80% of the patients, providing evidence of a proposed mechanism of VPA-induced hyperammonemia. Similarly, Latour et al.5 described a case series of six patients with severe epilepsy who were co-prescribed VPA and topiramate, with an exacerbation of hyperammonemia noted. The association of VPA and encephalopathy is also seen in a case series in which Gerstner et al.6 reported 19 new cases in Germany.

Other causes:

Urinary Tract Infections
Respiratory Tract Infections
Spontaneous Bacterial Periotonitis
GastroIntestinal bleeding
Viral Hepatitis

Common precipitating factors are as follows:13

Renal failure: Renal failure leads to decreased clearance of urea, ammonia, and other nitrogenous compounds.

Gastrointestinal bleeding: The presence of blood in the upper gastrointestinal tract results in increased ammonia and nitrogen absorption from the gut. Bleeding may predispose to kidney hypoperfusion and impaired renal function. Blood transfusions may result in mild hemolysis, with resulting elevated blood ammonia levels.

Infection: Infection may predispose to impaired renal function and to increased tissue catabolism, both of which increase blood ammonia levels.

Constipation: Constipation increases intestinal production and absorption of ammonia.

Medications: Drugs that act upon the central nervous system, such as opiates, benzodiazepines, antidepressants, and antipsychotic agents, may worsen hepatic encephalopathy.

Diuretic therapy: Decreased serum potassium levels and alkalosis may facilitate the conversion of NH4 + to NH3.

Dietary protein overload: This is an infrequent cause of hepatic encephalopathy.


The presence of Helicobacter pylori in the gastric mucosa represents another potential source of ammonia because this organism produces urease. Helicobacter ammoniagenesis may be most significant when accompanied by achlorhydria, in part due to increased absorption of nonprotonated ammonia across the gastric mucosa and, possibly, from increased numbers of bacteria. The role of H pylori in the pathogenesis of hepatic encephalopathy remains contentious; however, some investigators have identified it as an independent risk factor for the development of hepatic encephalopathy, while others have not.

One possible explanation for improvement in hepatic encephalopathy following eradication therapy for H pylori is that the Antibiotics decreased the gut's colonic population of urease-expressing organisms and those of the gastric mucosa. It appears reasonable to treat patients for H pylori when dictated by routine clinical circumstances (eg, in the treatment of peptic ulcer disease) but not as prophylaxis for hepatic encephalopathy.
We describe a case of an 82-year-old woman with a history of mild chronic liver disease who presented with hyperammonemic coma unresponsive to conventional therapy. Further investigation disclosed severe hypothyroidism. Thyroid hormone replacement resulted in gain of consciousness and normalization of hyperammonemia. In patients with an elevated ammonia level, altered mental status, and liver disease, who do not have a clear inciting event for liver disease decompensation, overwhelming evidence of hepatic decompensation, or who do not respond to appropriate therapy for hepatic encephalopathy, hypothyroidism should be considered and evaluated.



Ah-ha! The reason to use both L-Ornithine, and the Aspartate's together!!! Newport said what helped his father, was L-Ornithine, and magnesium/potassium aspartate.
I also just got a calcium aspartate. L-Aspartic acid is what the aspartate is--and also comes in a supplement by itself. I found it on

***Ornithine is a substrate for urea, and aspartate is a substrate for glutamine.****

Both enteral and intravenous administration of ornithine aspartate (a mixture of the 2 amino acids) are shown in some controlled trials to lower serum ammonia levels and improve mild hepatic encephalopathy by increasing the conversion of ammonia to urea.

Trials using ornithine alpha-glutarate did not demonstrate a benefit. In part, this may be because it only supplies one substrate for incorporation of ammonia. Relatively large doses of amino acids (18 g/d PO) appear to be necessary for any clinical benefit.

The mechanism of action of L-ornithine L-aspartate may extend beyond the urea cycle. Administration of ornithine aspartate to portal hypertensive rats results in high concentrations of glutamate in the plasma and CSF and an associated reduction in plasma ammonia.

The elevated glutamate concentrations facilitate synthesis of glutamine by glutamine synthase, which is expressed at high levels in the liver, brain, and skeletal muscle. This mechanism may permit further significant reductions in ammonia levels within both the CNS and the systemic circulation. Indeed, increased glutamine synthase expression is induced in skeletal muscle by portocaval shunting.

An increase in plasma concentrations of BCAAs also is an anticipated metabolic consequence of increased glutamate availability. It remains of uncertain significance and does not necessarily contribute to the improvement in hepatic encephalopathy documented in this experimental model.

Sodium benzoate also is shown to be efficacious in reducing serum ammonia. It is conjugated to glycine to form hippuric acid, which is excreted in the urine. Similarly, phenylacetate is conjugated with glutamine to form phenacetylglutamine. Both of these organic acids have been used successfully to treat hepatic encephalopathy in some clinical trials.

Zinc supplementation
The urea cycle allows conversion of ammonia to urea. Because 2 of the enzymes in this metabolic pathway require zinc as a cofactor and because reduced plasma zinc levels from increased urinary zinc losses are documented in hepatic encephalopathy, oral zinc supplementation is proposed for the treatment of hepatic encephalopathy.
The measurement of serum zinc levels may not accurately reflect whole-body zinc status, but it would appear reasonable to supplement patients found to have low serum zinc levels with zinc gluconate.

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