Ammonia is sometimes manufactured as a metabolic corrective when the body perceives itself to be in or nearing metabolic acidosis. Ammonia is extremely alkaline, and it can raise the systemic pH when we are in danger of metabolic acidosis, which can be life-threatening.
The problem is, the perception of the danger of metabolic acidosis is subjective, and tied very closely to the baseline pH of the brain. A brain that is TOO ALKALINE will perceive the threat of acidosis as TOO HIGH and produce TOO MUCH AMMONIA—which, in turn, keeps the brain too alkaline. Micro-dose LSD “acid” helped me with this vicious cycle. I have also seen a patent application for LSD to treat Alzheimer’s.
Glycine can be intolerable when there are problems clearing ammonia buildup. Taking amino acids like glycine taxes the urea cycle where ammonia is handled. Urea cycle issues—do they contribute to TRPV1 ACTIVATION? Intracranial hypertension and glutamine issues can be due to hyperammonemia.
Hyperammonemia primarily affects the brain, because excess ammonia readily crosses the blood–brain barrier and disrupts energy metabolism, neurotransmission, and osmotic balance. Regulating osmotic balance eats up a lot of vitamin B6; B6 deficiency can contribute to oxalate issues.
Symptoms of hyperammonemia range from subtle cognitive changes to life-threatening cerebral edema.
Early / Mild Elevation:
(blood ammonia modestly above normal, e.g. 40–80 µmol/L)
• Fatigue, lethargy
• Difficulty concentrating, poor attention span
• Irritability or mood changes
• Headache
• Nausea, vomiting
• Fine tremor or asterixis (flapping tremor) in some patients
Moderate Elevation:
(~80–150 µmol/L)
• Confusion, disorientation, “foggy thinking”
• Slurred speech
• Ataxia (unsteady gait)
• Visual disturbances, blurred or double vision
• Sleep–wake reversal (daytime somnolence, nighttime agitation)
Severe / Acute Crisis:
(>150–200 µmol/L; urea-cycle defect or acute liver failure)
• Stupor → coma
• Seizures (generalized or focal)
• Cerebral edema → raised intracranial pressure (papilledema, hypertension–bradycardia)
• Respiratory alkalosis from central hyperventilation (brainstem stimulation)
• Risk of brain herniation if not rapidly treated
Chronic/Subclinical Hyperammonemia:
(often seen in liver disease or partial urea-cycle defects)
• Minimal hepatic encephalopathy: subtle memory loss, slowed reaction time, poor executive function
• Personality changes, depression, irritability
• Episodic confusion or “brain fog” triggered by high protein intake,
GI bleeding, infection, or constipation
Pathophysiology Behind the Symptoms:
• Astrocyte swelling (cerebral edema)—ammonia
is converted to glutamine inside astrocytes, drawing water into the cells.
• Energy depletion – interference with TCA cycle and oxidative phosphorylation.
• Neurotransmitter imbalance – altered glutamate/GABA signaling, impaired urea cycle in brain.
