**11. Fatty acids**

**10.6. Vitamin E**

200 Pharmacology and Nutritional Intervention in the Treatment of Disease

apnea [10]1

**10.7. L-carnitine and Sleep**

Vitamin E has active ingredients of tocopherols and tocotrienols. It exists in eight different natural forms, all of which have antioxidant properties When supplemented it may reduce damage to cell DNA and cell and it has neuroprotective effect on the brain. Vitamin E may stabilize peripheral blood circulation, suppressing abrupt deformation of vessels [99], accel‐ eration of blood flow in vessels would increase the pressure of blood on the vessel walls, and subtle changes in vessel tension or shape might stimulate nerve fibres that are in anatomical proximity to the vessels [99]. Vitamin E normalized chronic sleep deprivation-induced reduction in the hippocampus GSH/GSSG ratio, and activity of catalase, super oxide dismutase (SOD), and glutathione peroxidase (GPx) [100]. Decreased levels of antioxidants and lower performance on the neuropsychological tasks were observed in patients with obstructive sleep

. This study suggests that an imbalance between antioxidants and pro-oxidants may

contribute to neuropsychological alterations in this patient population.During eight-year follow-up study to investigate the link between vitamin E, namely α-tocopherol, and memory disorders, it was found that higher total serum levels of vitamin E, and higher levels of γtocopherol, β-tocotrienol and total tocotrienols in particular, seemed to protect against memory disorders [102]. Their results show that the entire vitamin E family plays a role in memory processes. Accordingly, measuring the levels of vitamin E from serum is the most reliable way to determine whether they are sufficiently high. Limited research indicates that supplemental vitamin E may reduce symptom occurrence in restless leg syndrome [103].

Acetyl-L-carnitine (ALC) is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for β-oxidation [104]. Acetyl-L-carnitine can enter the brain, and the acetyl group helps form acetylcholine, an important neurotransmitter. L-carnitine enhan‐ ces resistance to oxidative stress by reducing DNA damage in Ataxia telangiectasia cells [105]. Positive results were seen in carnitine supplementation in depression, dysthymia, mental and physical energy, with less fatigue, muscle pain, and sleep problems [106,107,108]. Muscle weakness and hepatic dysfunction can also been noted [109]. Supplementation of carnitine has also been shown to be a mood elevator in the elderly [110]. Acetyl L-Carnitine helps the brain

Evidence for the effectiveness of L-carnitine in attention deficit and hyperactivity disorder (ADHD) has been studied [112]. Other studies in animals and human have shown that a combination of acetyl-L-carnitine and alpha-lipoic acid reversed many of the signs of aging and restored both physical and mental vigor. Low levels of carnitine are associated with a

L-Carnitine has been demonstrated to be therapeutic for individuals with narcolepsy. A recent study investigated the contribution of a gene polymorphism found in narcolepsy called CPT1B, which is important in fatty acid oxidation [114]. They found that individuals with narcolepsy had very low levels of serum acylcarnitine [115]. L-carnitine was given (510 mg/ day) to patients with narcolepsy it was revealed that total time for dozing off during daytime in narcolepsy patients, the primary endpoint, was significantly decreased by L-carnitine

form acetylcholine, a neurotransmitter needed for memory and thinking [111].

higher frequency of fragmented wakefulness [113].

There is a growing consensus that omega-3 fatty acids are essential nutrients for humans. Much of the evidence is based on physiological measurements such as neurological development and visual acuity. To better understand why this class of polyunsaturated fatty acids is required, we must determine the biochemical basis for the essentiality. Of the eight fatty acids that comprise the omega-3 metabolic pathway, the two that are most likely to have essential biochemical functions are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

EPA can be converted to prostaglandins, thromboxanes and lipoxygenase products [124]. However, no essential role for these EPA-metabolites has been reported, and it seems unlikely that the formation of these products is the reason that omega-3 fatty acids are essential. When elevated amounts of EPA are available, the incorporation of arachidonic acid (AA) into cell phospholipids and its conversion to eicosanoid mediators is reduced. Thus, EPA acts as a competitive inhibitor of AA, and this probably accounts for some of the beneficial effects of omega-3 fatty acids in the treatment of cardiovascular and inflammatory diseases. While the possibility that EPA is essential in order to modulate the effects of AA cannot be ruled out, the amounts ordinarily present in the plasma and tissues probably are too low to competitively inhibit the actions of AA. Therefore, modulation of AA metabolism is more likely to be a pharmacological effect of omega-3 fatty acid supplements rather than an essential physiolog‐ ical function.

The basis for considering DHA as the biochemically essential omega-3 component is much more compelling. DHA is the most abundant omega-3 fatty acid in most tissues, and it is present in large amounts in the brain and retina. DHA is the omega-3 fatty acid required for normal development of the nervous system and optimum visual acuity. Furthermore, when an omega-3 fatty acid deficiency exists, the body compensates by replacing it with the corresponding fatty acid of the omega-6 series, omega-6 docosapentaenoic acid (DPAn-6). These findings strongly suggest that DHA has an essential biochemical function. The most likely possibility is a membrane structural effect involving the packing of phospholipid head groups or the interaction of the lipid domains with membrane proteins. The lipids that contain the highest percentages of DHA are ethanolamine plasmalogen, phosphatidylethanolamine and phosphatidylserine. Therefore, it is likely that the function of DHA involves the metabo‐ lism, trafficking or physical properties of these phospholipids. Other possibilities that must be considered include the conversion of DHA to a lipid mediator, binding of DHA to a nuclear receptor that regulates gene expression, or formation of a DHA-centered free radical. It is thought that omega-3 fatty acids in fish oils may reduce inflammation of the brain and play a part in brain development and nerve cell regeneration [125]. However, there has been mixed evidence as to the benefits of omega-3 fish oils on the brain and whether they may protect against memory decline and dementia [126,127]. A combination of omega-3 fatty acid and vitamin B12 enriched diet may exert beneficial effects on synaptic plasticity and cognition, which may prove beneficial for mental health, particularly in preventing neurocognitive disorders [128].

and well-being. Fatty fish is the best source of omga-3 acids. One hundred grams of salmon contains about 1000 mg of omega-3 acids and 100 grams of herring contains about 2000 mg. White fish meat contains much less of these essential fatty acids than fish with fatty meat. Omega-3 acids have been tested in the treatment of subjects with attention deficit disorder and in subjects with depression, female subjects with borderline personality, fatigue in multiple sclerosis, memory disturbances, dementia and some other neuropsychiatric diseases. Some randomized controlled studies have shown that omega-3 fatty acids may ameliorate mental

Nutrition, Sleep and Sleep Disorders – Relations of Some Food Constituents and Sleep

http://dx.doi.org/10.5772/58345

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There is only little evidence showing that essential fatty acids may modulate sleep. In a small studied eight children. They were fed by total parenteral nutrition without essential lipids and seven other children who received a daily supplement of essential lipids in their parenteral nutrition. Slow wave sleep was significantly decreased in the group of children who did not receive fatty acids as compared to those who did. [138]No randomized clinical trials have been

Certain nutritional imbalances appear to influence sleep quality and play an important role

Zinc is an important cofactor for metabolism relevant to neurotransmitters, prostaglandins, and melatonin, and indirectly affects dopamine metabolism [139]. The role of zinc is thought to transduce oxidative stress and other signals converging at the production of nitric oxide into an specific intracellular response, suggesting an intriguing task of "signal transducer" [140]. It contributes to structure and function of brain [141], and low levels of zinc can cause a range of symptoms including hyperactivity and jitters [142]. Epidemiological studies on the influence of zinc/diet and lifestyle implications on degenerative disease and in particular on autism has been documented. Interestingly, antioxidant and micronutrients in the diet, such as zinc, influence the development and function of immune cells, the activity of stress-related proteins and antioxidant enzymes and help to maintain genomic integrity and stability [143, 144]. Zinc is included in many enzymatic processes. [145, 146] In CNS zinc is abundant in the so-called "zinc containing" synapses of glutamatergic neurons. Such neurons are located mainly in the prefrontal lobe. Frontal dysfunction may follow lack of zinc. On the other hand, bivalent zinc may cause excitotoxic damage. Also other minerals (e.g., magnesium, manga‐

Zinc was shown to play a role in inducing the synthesis of metallothionein that acts as a scavenger of metals and free radicals [149]. It is necessary for 100 different metalloen‐ zymes and metal–enzyme complexes [150], many of them in the central nervous system. Zinc supplementation of young children in low income countries improves their neurophy‐

nese) are important for proper functioning of the CNS. [145, 147, 148]

functions, but they are also conflicting results. [130 – 137]

done in primary insomnia or in central hypersomnias.

**12. Trace elements and sleep**

**12.1. Zinc**

in the maintenance of redox homeostasis:

A central question concerning the essentiality of omega-3 fatty acids is why DHA rather than the corresponding member of the omega-6 series, DPAn-6, fulfils this purpose. The usual Western diet contains 10-to 20-times more omega-6 fatty acid, and the same metabolic pathway is utilized by both fatty acid classes. One possibility is that DHA is utilized more efficiently than DPAn-6.

However, studies with neural cells in culture indicate that there is no appreciable difference in the uptake, retention or incorporation into phospholipids of DHA as compared with DPAn-6. While more detailed measurements may reveal a functional difference between DHA and DPAn-6, no such evidence is currently available. This suggests that DHA is utilized rather than DPAn-6 because it is more available to the tissues. Although the absolute amounts of these fatty acids in the plasma lipids are very small, there ordinarily is about five-times more DHA than DPAn-6. Furthermore, the main product formed by cultured astrocytes from omega-3 fatty acid precursors is DHA, whereas the main omega-6 product is AA. Astrocytes are the site where most of the polyunsaturated fatty acid precursors are elongated and desaturated in the brain. Thus, much more DHA than DPAn-6 appears to be available in the central nervous system [129].

#### **11.1. Fish oils and omega-3 fatty acids**

Polyunsaturated fatty acids (PUFA) are essential fatty acids in many mammals including humans. Both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are omega-3 acids and they may also be obtained by eating fish oils. There is some evidence showing that a reduced amount of ingested omega-3 fatty acids is associated with fatigue, depression and problems of attention. [130-136] A sufficient amount of PUFA from food is necessary for health and well-being. Fatty fish is the best source of omga-3 acids. One hundred grams of salmon contains about 1000 mg of omega-3 acids and 100 grams of herring contains about 2000 mg. White fish meat contains much less of these essential fatty acids than fish with fatty meat. Omega-3 acids have been tested in the treatment of subjects with attention deficit disorder and in subjects with depression, female subjects with borderline personality, fatigue in multiple sclerosis, memory disturbances, dementia and some other neuropsychiatric diseases. Some randomized controlled studies have shown that omega-3 fatty acids may ameliorate mental functions, but they are also conflicting results. [130 – 137]

There is only little evidence showing that essential fatty acids may modulate sleep. In a small studied eight children. They were fed by total parenteral nutrition without essential lipids and seven other children who received a daily supplement of essential lipids in their parenteral nutrition. Slow wave sleep was significantly decreased in the group of children who did not receive fatty acids as compared to those who did. [138]No randomized clinical trials have been done in primary insomnia or in central hypersomnias.
