The nutritional requirements of most interest to patients with sleep disorders associated with fibromyalgia and depression are nutrients which function as precursors of neurotransmitters that modulate circadian effects on the sleep-wake cycle and autonomic nervous system activity (Boivin DB. J Psychiatry Neurosci 2000). In addition to tryptophan, low blood levels of choline and GABA have been noted in patients with sleep disorders indicating that the needs for choline and glutamate are not being met at the current levels of intakes of these patients (Wurtman RJ. Clin Neuropharmacol 1988). A dietary deficiency of choline has been associated with sleep apnea syndromes and disorders of restorative sleep (Anderson GH, Johnston JL; Can J Physiol Pharmacol 1983). Plasma levels of glutamate have been found to be a highly significant discriminatory variable for identifying patients with major depression (Altamura C, Maes M, Dai J, Meltzer HY; Eur Neuropsychopharmacol 1995). The insensitivity of acetylcholine and serotonin to circulating levels of GABA observed in patients with sleep disorders suggests impaired control of the normal sleep/wake cycle which may be related to imbalances among these neurotransmitters resulting from inadequate intakes of their nutrient precursors (Mendelson WB;J Clin Psychiatry 2001).

As precursors of serotonin and acetylcholine, tryptophan and choline are especially important to these patients as is glutamate which functions not only as a neurotransmitter but also as a precursor of GABA.  The concept that nutrient requirements are modified by disease has been recognized for more than 30 years, and is supported by studies which have shown changes in plasma, urinary, and tissue levels of nutrients associated with abnormalities in physiological endpoints reflective of specific pathologies (Lipincott Williams & Wilkin, 2006). These requirements can be estimated by determining the level of intake at which a physiological response is improved indicating that the balance between intake and metabolic demand has been favorably modified. The nature of the pathological characteristics of a disease will determine the relative amounts of nutrients needed to restore balance between intake and demand (Anderson GH, Johnston JL. Can J Physiol Pharmacol 1983). The degree of coordination between the activities of different neurotransmitters is an important consideration in assessing the amounts of dietary precursor needed (Anderson IM, Mortimore C ,Adv Exp Med Biol 1999).

Diseases with pathologies that involve imbalances in neurotransmitters will increase the requirements for certain amino acids and other dietary precursors to restore homeostasis (Bazzichi L, Palego L, Giannaccini G et al; Clin Biochem 2009). For most of these amino acids and dietary precursors, uptake by target neurons is a concentration-driven process; therefore, intakes must be sufficient to increase the extracellular to intracellular concentrations to levels high enough to drive a rapid rate of uptake (Fernstrom JD; J Am Diet Assoc 1994;94). The rate of precursor uptake by target neurons is important to neurotransmitter synthesis because the enzymes involved are found only in these neurons and thus the amount of substrate available is the limiting factor in neurotransmitter production (Wurtman RJ, Hefti F, Melamed E; Pharmacol Rev 1980). As blood levels of dietary precursors rise in response to increased intakes, the concentration-driven rate of precursor uptake by target neurons is increased, making more substrate available for neurotransmitter production and subsequent release . Changes in intakes of dietary precursors of these neurotransmitters will therefore influence physiological responses by affecting neurotransmitter availability (Fernstrom JD, Fernstrom MH;Nutr Rev 2001)

A large body of peer-reviewed published data supports the basis for increased requirements of tryptophan, glutamate, and choline in conditions  which depend on neurotransmitter balance. Patients who show decreased blood levels of certain amino acids despite maintaining their usual protein intake may find that Rx only medical foods can help address the deficiency of  amino acids that are selectively increased as a result of specific physiological requirements associated with their disease (Hasselmo ME, Fehlau BP;J Neurophysiol 2001). Rx only medical foods can help patients suffering from sleep disorders address the competitive demands for certain amino acids. Increasing the availability of precursor molecules can imporve the supply of neurotransmitters available that regulate and maintain the various sleep cycles.