Precursor Amino Acid Therapy

A new entry into pain management

In recent years, the use of amino acids have been used rather widely in the fields of sports medicine, weight control, psychiatry, and addiction medicine. They are now increasingly being used by pain practitioners. Consequently, this journal is publishing a series of articles on amino acids, diet, and other nutritional adjuncts. Although we recognize that there are few controlled studies, pain practitioners are consistently reporting and advocating a variety of natural supplements and dietary measures as adjuncts to standard medical treatments. This article deals with the concept of precursor amino acids therapy.

What Is Precursor Amino Acid Therapy?

The scientific and medical launching of precursor amino acid therapy can be traced to the work of Richard Wurtman and colleagues at the Laboratory of Neuroendocrine Regulation, Massachusetts Institute of Technology (MIT).1,2 Wurtman used the term “precursor” to label certain amino acids which were the initial chemical building blocks in metabolic pathways. He singled out three amino acid precursors—choline or lecithin, tryptophan, and tyrosine as prime examples of precursor control of critical neurotransmitters—and called for clinical trials. A compelling argument was the demonstration that a tryptophan loading dose increased rat brain serotonin levels as demonstrated by fluorescent staining of tissue.

Since that time, two of the three amino acid precursors Wurtman’s initially advocated—tyrosine and tryptophan—have found great support in clinical practice. The use of choline-lecithin has not. So important are the metabolic pathways for these precursors that they are shown in Figure 1.

Since Wurtman’s early work, many clinicians have engaged in the practice of precursor-amino acid therapy. Most have been in the psychiatric, weight control, and chemical dependency fields.3-5 Only recently have pain practitioners begun to use precursor amino acid therapies so the clinical reports are few in number. Table 1 lists possible symptoms presenting if the end products of the three metabolic pathways illustrated in Figure 1 are deficient.

Table 1. Possible deficiency symptoms with lack of neurotransmitters
Tryptophan to Serotonin Glutamine to Gaba Tyrosine to Epineprine
Insomnia Muscle Spasm Fatigue
Depression Pain Depression
Pain Anxiety Pain
Obesity   Apathy

Glutamine to Gamma Amino Butyric Acid (GABA) Pathway

In addition to the use of tyrosine and tryptophan as a precursor amino acids, a third popular precursor amino acid therapy has emerged: gamma amino butyric acid (GABA).5 GABA is a major neuroinhibitor in the central and peripheral nervous systems. Its adequate supply and function is critical for pain control. Physicians routinely prescribe pharmaceutical agents which mimic GABA activity by various mechanisms. Included are benzodiazepines, gabapentin, and pregabalin. Glutamine is the dietary amino acid that is the precursor of GABA (see Figure 1).

Figure 1. Three Precursor Amino-Acid Pathways

Physicians can administer either a glutamine precursor or pure GABA to reduce pain, anxiety, or promote muscle relaxation. The compounds can be used in conjunction with a benzodiazepine or other agent that mimics the activity of GABA. Glutamine and GABA are widely available in tablet or capsule form. GABA can be obtained as a sub-lingual preparation with starting oral dosages in the range of 1000 to 2000mg each day.

Tyrosine to Epinephrine Pathway

Often known as the catecholamine pathway, the end-compounds dopamine, norepinephrine, and epinephrine are well known to be involved with energy, fatigue, thermogenesis, motivation, and depression. They may also have a direct interaction with pain modulation. Consequently, an adequate concentration of these compounds in biologic fluids is critical. Tyrosine and its precursor phenylalanine are inexpensive and available as oral tablets and capsules with a starting daily dosage usually ranging from 1000 to 2000mg.

Tryptophan to Serotonin-Melatonin Pathway

Tryptophan is perhaps the best-known amino acid precursor due to its wide scale use in the 1980’s for weight control, depression, and insomnia. Serotonin is known to be related to pain modulation, so tryptophan and its metabolite 5-hydroxy tryptophan are increasingly being used for pain control. The starting daily dosage of tryptophan is in the range of 1000 to 2000mg a day.

The end product of its metabolic pathway is melatonin. It is widely used for sleep and by travelers for time-zone adjustment. It is marketed in tablets ranging from 1 to 10mg and can be used with other sleep medications. We find the sleep dosage in pain patients to be in the range of 5 to 20mg.

It is noted that tryptophan was removed from the over-the-counter, dietary supplement market in 1989 due to some contaminated products. It has now, however, returned to the dietary supplement market.

Cautions and Disclaimer

It is cautioned that precursor amino acids are not a substitute for standard medical therapy but an adjunct. Also, the pain practitioner must use amino acids on a purely clinical trial basis. Dosages are not standard, and there are essentially no random, double-blind studies that meet the evidence-based criteria of a prescription-approved product. Amino acids can’t be patented and so, without economic motivation, there will likely be no future wide-scale controlled trials.

On a practical note, precursor amino acids must be taken with cold fluids on an empty stomach otherwise they may be digested as food. Most practitioners who recommend amino acids also suggest that vitamin B-6 supplements be taken con-currently since this vitamin is a critical co-factor in amino acid metabolism.

Summary

Three precursor amino acid therapies are widely used in some fields of medical practice. They are just starting to be used by pain practitioners as adjuncts to standard, medical therapy because de-ficiencies result in significant symptoms (see Table 1). Use of precursor amino acids is inexpensive, safe, and may enhance standard pain treatment. The end compounds of the three most widely used precursor amino acids, GABA, serotonin, and epinephrine, have such well-known biologic actions that pain practitioners should seriously consider incorporating precursor amino acid therapy into their current clinical regimens.

First published on: May 1, 2009