Recovery of sleep-wake cycle and related chronic fatigue syndrome


Sleep is a fundamental need for every individual, so much so that its deprivation leads to disorders such as increased fatigue, excessive daytime sleepiness, difficulty concentrating and irritability [26,17,18]. The causes of sleep problems are varied and include: psychosocial stress, psychiatric disorders (depression, anxiety), medication, sleep apnoea, environmental disorders and persistent activation of the Sympathetic Nervous System (ANS-PPG Stress Flow). The consequences of poor rest should not be underestimated as these disorders can have significant negative effects on health and quality of life. In particular, the link between sleep disorders and a strong feeling of tiredness is very frequent; a good strategy to mitigate this problem is the supplementation with nutrients that are useful to improve the quality of sleep as well as to ensure sufficient energy production and a decrease in the feeling of tiredness. The combined supplementation of a product for evening use containing a dry extract of hops (Humulus lupulus L.), whose therapeutic properties are well documented not only for sleep-wake cycle problems but also for mood disorders, and a supplement taken before breakfast containing Coenzyme Q10 and L-carnitine combined with minerals, vitamins and essential substances for cellular energy production, is a multi-pronged action strategy.

Sleep disorders and effect on circadian rhythms that regulate sleep

Sleep is an essential requirement for survival, as its deprivation alters biological rhythms. Various studies suggest that it is needed to “restore the brain”, as the cortex is the only organ that can rest only during sleep. Conventional medical treatment includes psychological and pharmacological approaches, but in the long term the use of drugs can lead to addiction, problems related to withdrawal symptoms and side effects. Therefore, natural approaches are gaining increasing popularity as they do not have the drawback of many drugs. Although the active principles responsible for the therapeutic effects are still being investigated, it appears that the sedative activity is mainly due to the α-acid, 2-methyl-3-buten-2-ol [27,28,29]: the mechanism of action involves increasing the activity of the inhibitory neurotransmitter GABA by modulating GABA(A) receptors in the brain [30,31,32,33]. Hop extract has been shown to have important activities on the circadian rhythms that regulate sleep: it affects serotonin and melatonin [34,35,36]. The effects of hop extract are comparable to those of melatonin, since the hypothermic action of melatonin and hop extract can be antagonised by luzindole (a competitive antagonist of melatonin receptors), suggesting that the soporific properties of hop extract are mediated by the activation of melatonin receptors [37,38]. The active compounds responsible for the soporific action include β-bitter acids, myrcenol and xanthohumol [34]. According to literature, hops can improve the neuroendocrine response of the CNS by interacting with GABA, serotonin and melatonin receptors, thus having an effective sedative effect that modulates the sleep-wake cycle and promotes the induction of sleep [34].

Mood disorders, anxiety states and antidepressant activity

Since psychosocial stress and psychiatric disorders (depression, anxiety) are also among the causes of sleep disorders, it is worth mentioning that hop shoots were also used in the past for their sedative properties in the treatment of obsessive behaviour, rumination and worry. Data have shown that hop extract offers better sedation, pre-anaesthesia and anti-anxiety effects than diazepam [39]. Humulus lupulus L. extract also exerts an important antidepressant activity through alpha-acid compounds [40]: in preclinical studies, the administration of these compounds not only proved the effectiveness of hops in sleep disorders, but it was also assumed that these molecules may represent a new class of compounds for the development of natural antidepressant products. Based on clinical studies and on literature, hop preparations have proven to be useful alternatives in the management of stress and anxiety in daily life [41].

Energy production

Coenzyme Q10 (CoQ10) is an organic molecule that plays a dual role: as an antioxidant and a bioenergetic compound (useful for energy production) [1]. A deficiency in CoQ10 causes both respiratory chain disorders, leading to changes in energy metabolism, and a decrease in mitochondrial membrane potential, which in turn induces apoptosis. The causes of its deficiency are linked to various factors: lack and/or loss of skeletal muscle mass (S-Score - BIA-ACC), mutation of the gene responsible of its synthesis, inhibition of HMG-CoA reductase biosynthesis, intake of statins, ageing and chronic degenerative diseases [2]. L-carnitine is another important factor in cellular energy metabolism. It is distributed throughout the body but the highest concentrations are found in the most active metabolic tissue, such as the myocardium and the skeletal muscle; it is biosynthesised within the human body using the amino acids L-lysine and L-methionine and is present in many food types such as red meat. L-carnitine is essential for the transport of long-chain fatty acids across the inner mitochondrial membrane to their oxidation site, where energy is produced in the form of ATP; one of the most important consequences of carnitine loss is the alteration of the metabolic pathways leading to energy production [3,4,5]. In biochemical processes such as cellular respiration, DNA and RNA replication, the maintenance of cell membrane integrity and the blocking of free radicals, some minerals such as copper and zinc play a crucial role: the presence of free radicals alters membrane integrity, increases the risk of cancer and accelerates the ageing process; copper and zinc are cofactors of enzymes such as superoxide dismutase, involved in the reduction of superoxide radicals. These two minerals can also improve protection against cellular stress by stabilising cellular proteins so that they are less susceptible to oxidation [6,7,8,9].

Reduced feeling of tiredness

In studies on elderly subjects, administration of L-carnitine resulted in a progressive increase in skeletal muscle mass (S-Score - BIA-ACC) and a simultaneous significant reduction in muscle fatigue. The body’s carnitine concentration tends to decrease in parallel with the loss of skeletal muscle mass, an event that occurs particularly with age; administration of levocarnitine stimulates a reduction in adipose tissue (Fat Mass - BIA-ACC), an increase in skeletal muscle mass, improves physical and cognitive abilities and reduces the feeling of fatigue [13]. In other studies, small doses of L-carnitine have been shown to be beneficial in haemodialysis patients with pain, muscle weakness, fatigue and cramps: after 12 weeks of treatment, approximately two thirds of the patients experienced an improvement in muscle symptoms, suggesting that prolonged administration of small doses of L-carnitine may improve muscle symptoms associated with dialysis [14,15]. Vitamin D is often considered only for its effect on calcium metabolism and bone morphology, however its action affects the whole body [19]: cell growth, carcinogenesis, immune function, cardiovascular physiology and skeletal muscle [20,21,22]. It has been demonstrated that vitamin D deficiency contributes to the loss of muscle strength [23]: studies show that vitamin D supplementation leads to an improvement in muscle performance and a reduction in falls [24]. Furthermore, numerous observational studies, particularly in elderly subjects, indicate that vitamin D is positively correlated with muscle strength and physical performance and inversely associated with the risk of loss of balance [25].


Simple, targeted strategies to support deficiencies or correct minor lifestyle mistakes can be of considerable help; for example, choosing a diet that favours a higher calorie load during the day and a lower one in the evening, together with drinks or hot food to activate the parasympathetic nervous system (PPG Stress Flow) and thus bring the body to a resting state, can provide great benefits; In addition, targeted supplementation with a combination of several elements to ensure better sleep quality, sufficient energy production and a reduction in the feeling of tiredness can support the improvement of sleep-wake rhythm problems. Supplements (taken in the evening) containing highly titrated extract of hops support emotional disorders, related problems such as loss of sleep-wake rhythms and chronic stress, while supplements (taken before breakfast) combining the properties of coenzyme Q10 and L-carnitine with minerals such as copper and zinc provide the body with the correct amount of minerals, vitamins and essential substances to ensure sufficient energy production and reduce the feeling of tiredness.

Author: Dario Boschiero - Date: 02/02/2021

Attention: these contents can be freely used for personal learning purposes only. The use is regulated by Law No. 633/1941 and subsequent amendments, as well as by the copyright and patent legislation in force. Any use for commercial and profit-making purposes is forbidden.


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