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Pyroglutamate (PCA)

Pyroglutamate (also called 2-oxo-pyrrolidone carboxylic acid, or PCA) is an amino acid naturally occurring in vegetables, fruits, dairy products, and meat, and seems to be an important flavor constituent in these foods. It is also normally present in large amounts in the human brain, cerebrospinal fluid, and blood. Pyroglutamate is known to have a number of remarkable cognitive-enhancing effects.

After oral administration, pyroglutamate passes into the brain through the blood-brain barrier and stimulates cognitive functions. Pyroglutamate improves memory and learning in rats, and has anti-anxiety effects in rats (Pearson and Shaw, 1988).

Pyroglutamate has also been shown to be effective in alcohol-induced memory deficits in humans (Sinforiani, 1985) and, more recently, in people affected with multi-infarct dementia (Scoppa, in press). In these patients, the administration of pyroglutamate brought about a significant increase of attention and an improvement on psychological tests investigating short-term retrieval, long-term retrieval, and long-term storage of memory. A statistically significant improvement was observed also in the consolidation of memory.

In human subjects, pyroglutamate was compared with placebo in a randomized double-blind trial for assessing its efficacy in treating memory deficits in 40 aged subjects. Twenty subjects were treated with pyroglutamate and 20 with placebo over a period of 60 days. Memory functions were evaluated at baseline and after 60 days of treatment by means of a battery made up of six memory tasks. The results show that pyroglutamate is effective in improving verbal memory functions in subjects affected by age-related memory decline (Grioli, 1990).

In Italy, arginine pyroglutamate (one source of pyroglutamate) is used to treat senility, mental retardation, and alcoholism (Anderson, 1987). Arginine pyroglutamate is simply an arginine molecule combined with a pyroglutamate molecule. Arginine alone does not produce cognitive enhancing effects. It is likely that pyroglutamate is the active ingredient of arginine pyroglutamate.

Some people use arginine, a single amino acid, to build muscle bulk and to burn fat because the arginine causes the pituitary gland to release natural growth hormone. Arginine pyroglutamate, in addition to having cognitive enhancing effects, is an excellent growth hormone releaser because it is carried more efficiently across the blood-brain barrier than arginine alone (Filipo, 1987).

Many people have told us that they like the effects of arginine pyroglutamate a great deal. Some of the more interesting anecdotes are listed in Appendix D (see page 179).

Precautions: No serious adverse effects from the use of pyroglutamate, or from the use of arginine pyroglutamate, have been reported. Arginine and pyroglutamate are amino acids found commonly in natural foods and consumed by most people on a regular basis.

Dosage: 500mg to 1000mg per day for arginine pyroglutamate or somewhat less if straight
pyroglutamate is used.

Sources: NutriGuard Research carries a high-quality, inexpensive PCA product (see appendix A for their number.) Health food and vitamin stores also offer various products containing pyroglutamate. Arginine pyroglutamate (one source of pyroglutamate) is often used for its growth-hormone releasing effect, but is still effective as a cognitive enhancer in this form. Other names for pyroglutamate include: alpha-aminoglutaric acid lactam, glutamic acid lactam, glutimic acid, glutiminic acid, pyroGlu, and pyroglutamic acid. Other names for arginine pyroglutamate include: Adjuvant, Piraglutargine, Arginine Pidolate.


Anderson, K., Anderson, L. Orphan Drugs. Los Angeles, CA: The Body Press, 1987, p. 170.

Cenni, A., et al. "Pharmacological Properties of a Nootropic Agent of Endogenous Origin: D-Pyroglutamic Acid." Journal of Drug Development. 1988, 1, pp. 157-62.

Chemical Business. September 1988, p. 43.
Drago, F., Continella, G., Valerio, C., D'Agata, V., Astuto, C., Spardaro, F., Scapagnini, U. "Effects of Pyroglutamic Acid on Learning and Memory Processes of the Rat." Acta Therapeutica. 1987, Vol. 13, pp. 587-94.

Filippo, V., Spignoli, G., Isidori, A. "Effects of Arginine Pyroglutamate on Growth Hormone in Children." Clinical Trials Journal. 1987, Vol. 24, pp. 387-90.

Grioli, S. et al. "Pyroglutamic Acid Improves the Age Associated Memory Impairment." Fundamental and Clinical Pharmacology. 1990, Vol. 4, pp. 169-73.

Moret, C., Briley, M. "The Forgotten Amino Acid Pyroglutamate." Trends in Pharmacological Sciences. 1988, Vol. 9, pp. 278-9.

Paoli, F., Spignoli, G., Pepeu, G. "Oxiracetam and D-Pyroglutamic Acid Antagonize a Disruption of Passive
Avoidance Behavior Induced by the N-Methyl-Aspartate Receptor Antagonist 2-amino-5-phosphonovalerate."
Psychopharmacology. 1990, 100, pp. 130-1.

Pearson, D., Shaw, S. Durk Pearson & Sandy Shaw's Life Extension Newsletter. October 1988, Vol 1, Number 8, p. 65-66.

Pepeu, G., Spignoli, G. "Neurochemical Actions of Nootropic Drugs". Advances in Neurology. Vol. 51:
Alzheimer's Disease. New York: Raven Press, Ltd., 1990.

Porsolt, R.D., Lenegre, A., Avril, I., Parot, P., Tran, G. "Antiamnesic Effects of Magnesium Pyrrolidone
Carboxylate (MAG 2) in Three Models of Amnesia in the Mouse." Drug Development Research. 1988, 13, pp.

Sinforiani, E., Trucco, M., Cavallini, A., Gualtieri, S., Verri, A.P., Spignoli, G. "Sulla Reversibilita Dei Disordini Cognitivi Negli Alcolisti Cronici In Fase Di Dissauefazion." Minerva Psichiatrica. 1985, 26, pp. 339-42.

Spignoli, G., Magnani, M. Pepeu, G. "Pyroglutamic Acid Antagonizes the Amnesic Effect and the Decrease in
Brain Acetylcholine Level Induced by Scopolamine." Pharmacological Research Communications. 1987, Vol. 10, pp. 901-7.

Excerpts from "Smart Drugs & Nutrients;
How to Improve Your Memory and Increase Your Intelligence
Using The Latest Discoveries in Neuroscience"
By Ward Dean, M.D., and John Morgenthaler