Glutamic Acid, Gamma-Aminobutyric Acid and Glutamine – The Brain’s Three Musketeers
Glutamic Acid (GA) is a nonessential amino acid which can normally be synthesized in the body from many substances, i.e., alpha ketoglutarate, ornithine, arginine, proline, or Glutamine (GAM). GA is used to make proteins, peptides (glutathione), amino acids (proline, histidine, GAM, and GABA) and DNA. GA, GABA (gamma-aminobutyric acid) and GAM are all neurotransmitters in the brain. GA is excitatory and GABA inhibitory. GAM is primarily a brain fuel. Vitamin B6 and manganese increase the amount of GABA made from GA. Aspartic acid is an excitatory neurotransmitter that is competitively transported with GA, whereas taurine and glycine are inhibitory neurotransmitters that are competitively transported with GABA.
GA and GAM are extremely abundant amino acids. GA is the second most concentrated in the brain and GAM is not far behind. GAM is the most abundant amino acid in blood. GA is the most abundant in food; about 7 grams are contained in a cup of cottage cheese and as much as 13 grams in a pound of pork.
Initial studies with GA using 10 to 12 g in mentally retarded individuals were found to raise IQ. Doses of GABA 1 to 3 g orally also have been used effectively to raise the IQ of mentally retarded persons.
Initial studies in alcoholics using a daily dose of 10 to 15 g of L-GAM were effective in controlling this addiction. These results, have not been carefully reproduced, but suggest therapeutic promise.
GAM is a major fuel for the brain, but also for lymphocytic cancer cells. An enzyme which destroys GAM is useful in acute leukemia and other cancers, Some effects of the excessive breakdown of GAM are infertility, depression, abdominal cramps, headache, weight loss, anorexia, increased blood ammonia and, rarely, a Parkinson’s syndrome. Other deficiencies of the glutamate family of neurotransmitters relate to the metabolism of glutathione.
GA given as MSG can produce a seizure-like disorder in infants. In contrast, various drugs that inhibit GA, aspartic acid and metabolites are effective anticonvulsants. GABA is found to be deficient in cerebrospinal fluid and brain in many studies of experimental and human epilepsy. Benzodiazepines (such as Valium) are useful in status epilepticus because they act on GABA receptors. GABA increases in the brain after administration of many seizure medications. Hence, GABA is clearly an antiepileptic nutrient, while the data is mixed regarding GA. Inhibitors of GAM metabolism can also produce convulsions.
Spasticity and involuntary movement syndromes, e.g., Parkinson’s, Friedreich’s ataxia, tardive dyskinesia, and Huntington’s chorea are all marked by low GABA when amino acid levels are studied. Trials of 2 to 3 g of GABA given orally have been effective in various epilepsy and spasticity syndromes.
Agents that elevate GABA also are useful in lowering hypertension. Three grams orally have been effective in control of blood pressure. GABA is decreased and GA is increased in various encephalopathies. GABA can reduce appetite and is decreased in hypoglycemics. GABA reduces blood sugar in diabetics. Chronic brain syndromes can also be marked by deficiency of GABA, as well as of GA and GAM. GABA has many promising uses in therapy.
There may be therapeutic uses of GA and GAM, but GABA has the most therapeutic potential of the “three musketeers.” GABA levels are difficult to detect in plasma and urine, while GAM and GA are easily measured. GABA therapy should be considered when GA is elevated and GAM is deficient. Cerebrospinal fluid levels of GABA may be useful in diagnosing very serious diseases. Vitamin B6, manganese, taurine and lysine can increase both GABA synthesis and effects, while aspartic acid and GA probably inhibit GABA effects.
GABA, GA and GAM are likely to provide an even greater therapeutic potential in the near future.
Proline and Hydroxyline – Collagen Constituents
Proline and hydroxyproline are nonessential amino acids that are highly concentrated throughout the body, except in cerebrospinal fluid. Collagen is an important protein, and is the major reservoir for these amino acids. Proline can be synthesized in the body from either ornithine or glutamic acid; it can be broken down into ornithine and thereby reduce the body’s requirements for ornithine and arginine.
Excess proline due to genetic errors can lead to convulsions, elevated blood calcium and osteoporosis. Dietary restriction is a useful treatment, probably because the body depends on dietary proline to meet some of its proline needs. Therefore proline deficiency probably can occur under some conditions. At least one patient with Parkinson’s disease with low blood levels of proline has been identified at the Brain Bio Center.
Elevated proline levels can occur in alcoholics with cirrhosis and probably in depression and seizure disorders. We have observed elevated hydroxyproline levels in cases of psychotic depression. These patients also may require extra vitamin C.
Proline is modified in smokers and becomes a carcinogen. Drugs which inhibit proline metabolism have anticancer properties. Low proline diets may be useful in some forms of cancer treatment.
Proline also may be of value in wound healing. Proline peptides are involved in important neurological proteins.
Knowledge of proline supplementation is limited. Proline is concentrated in high protein foods like meat, cottage cheese and wheat germ. There is more proline in dairy protein than in meat protein, whereas for most other amino acids, the reverse is true.
Aspartic Acid – Asparagine – Important Metabolic Pathways
Aspartic acid is a nonessential amino acid which is made from glutamic acid by enzymes using vitamin B6. The amino acid has important roles in the urea cycle and DNA metabolism. Aspartic acid is a major excitatory neurotransmitter, which is sometimes found to be increased in epileptic and stroke patients. It is decreased in depressed patients and in patients with brain atrophy.
Aspartic acid supplements are being evaluated. Five grams can raise blood levels. Magnesium and zinc may be natural inhibitors of some of the actions of aspartic acid.
Aspartic acid, with the amino acid phenylalanine, is a part of a new natural sweetener, aspartame. This sweetener is an advance in artificial sweeteners, and is probably safe in normal doses to all except phenylketonurics. The jury is still out on the long term effects it has on many brain neurohormones.
Aspartic acid may be a significant immunostimulant of the thymus and can protect against some of the damaging effects of radiation. Many claims have been made for the special value of administering aspartic acid in the form of potassium and magnesium salts. Since aspartic acid is relatively nontoxic, studies are now in progress to elucidate its pharmacological and therapeutic roles.