**9. Dietary nutrients and sleep**

Sleep, a complex phenomenon, is not merely the result of physical fatigue or decrease in activity; instead it is a complicated behavioural state requiring the integration of several neuronal processes. Prostaglandins (PGs) are ubiquitously distributed in mammalian tissues, exerting a variety of physiological and pathological effects such as disaggregation of blood platelets [46], relaxation of smooth muscle [47] and pain and inflammation [48]. It is generally accepted that PGD2 is one of the major PGs unique to the CNS, when compared to the relatively low concentrations present in peripheral tissue [49]. Studies have revealed a variety of endogenous substances that convincingly induce sleep. Among the multitude of sleeppromoting substances, PGD2 has been described as a somnolence promoting substance in the adult rat by acting on the traditional sleep centres of the VLPO area. PGD2 is produced from PGH2 precursor by enzyme PGDS that is predominately synthesised in the leptomeningeal

Prostaglandin D2 (PGD2) is a biologically active primary prostaglandin and a common product of arachidonic metabolism in mammals. As a major eicosanoid product of mast cells PGD2 is released in large quantities during allergic and asthmatic anaphylaxis. Several studies have reported a crucial role for the prostaglandin D system in sleep regulation. This PGD2 accumulates in the cerebrospinal fluid (CSF), where it induces physiologic sleep in rats and humans. PGD2 and PGE2 are found in high concentrations in the hypothalamus compared to other regional areas of the brain [50, 51]. In addition, marked elevations of endogenous PGD2 concentrations in CSF occur in patients who suffer African sleeping sickness [52]. Continuous infusion of PGD, into the lateral cerebral ventricle of monkeys during the diurnal period induced a sleep pattern similar to physiological night sleep [53]. It is involved in the regulation of reducing body temperature in sleep [54]. It is also produced in the brain via an alternative pathway involving a soluble, secreted PGD-synthase also known as β-trace [55]. PGD2 acts in the central nervous system in sleep induction and lowering of body temperature [51].Further pharmacological actions include inhibition of platelet aggregation and relaxation of vascular

Glutathione is a tripeptide (gamma-glutamylcysteinylglycine) that performs many vital functions in every cell of the body [57]. It is present in two forms in the body; in a "reduced (GSH)" or an "oxidized (GSSG)" form. The majority of glutathione in the body is present in its reduced form because this is the only way it can perform its critical role. Certain tissues are more susceptible to GSH depletion than others. The reduced form of glutathione is the most active form and is found in healthy cells. GSH plays an important role in the protection of cells against damage from free radicals and other electrophiles. Several steps in the metabolism of arachidonic acid may be normally regulated by GSH-enzymes [58]. It was an early observation that GSH may function as a chemical cofactor or coenzyme in the formation of some PGs, particularly PGEs [59]. Measuring glutathione levels in specific areas of the brain of sleepdeprived animals reveals that the thalamus and hypothalamus are particularly susceptible [60]. It is essential for detoxifying cells and this process is more active during sleep [61]. The

layers and CP of the brain.

196 Pharmacology and Nutritional Intervention in the Treatment of Disease

smooth muscle [56].

**8. Glutathione and sleep**

In a recent large survey on more than 4500 people the association of many different nutrients to sleep were studied. [66] The nutrients associated with difficulty falling asleep in order of importance were lack of alpha carotene, lack of selenium, lack of dodecanoic acid, lack of calcium and increased hexadecanoic acid. [66]Difficulty maintaining sleep was associated with increased use of salt, less butanoic acid, less carbohydrates, less dodecanoic acid, less vitamin D, less lycopene, more hexanoic acid and more moisture. Non-restorative sleep was associated with more butaneoic acid less calcium, less vitamin C, less plain water, more moisture and more cholesterol. In the same survey increased daytime sleepiness was associated more moisture, more theobromine (see above for caffeine), less potassium and less plain water. [66]
