For a long time, it was believed that sleep is a state of the organism in which most of its functions cease, and the body is completely at rest. Today we know that this is not entirely true, because even though when we close our eyes and fall asleep some processes in the body slow down, others remain surprisingly active. Sleep begins with the activation of an area of the brain called the hypothalamus, where cascading changes occur that induce changes in the body that result in sleep. Nerve cells in the brain reduce alertness and promote sleepiness, while electrical activity in the brain begins to slow. These and other changes that occur as sleep continues to affect nearly every cell in your body.1
In modern society, there is increasing concern about the risks associated with insomnia and lack of sleep. Recent epidemiological data support the opinion that many segments of the adult population are chronically sleep deprived. On the other hand, there are experts who claim that our basic required amount of sleep is about 6 hours during one night, and that we can easily forget more sleep, because it is completely unnecessary. However, experimental data on the effects of both acute and cumulative partial sleep deprivation (PSD) consistently point out that sleep restriction has significant negative effects on sleepiness, motor and cognitive performance and mood as well as on some metabolic, hormonal and immunological variables.
Given that chronic partial sleep deprivation can have serious, long-term adverse health effects, it should be avoided in the general population. In the short term, the effects of sleep restriction appear to accumulate linearly, while the effects of long-term PSD should be further investigated, as the few available studies are flawed by methodological weaknesses.
On the other hand, there is evidence that extending sleep by 2-3 hours beyond the norm brings only marginal benefits to the average individual. Finally, it is underlined that, as large individual differences do exist in the need for sleep, the search for the sleep need may be vain. A somnotypology, taking into account age, gender and the position in both the sleep-alert and the morningness-eveningness continuum, should help in the search for the actual individual sleep need.2
Insomnia and sleep disorders are considered a major problem worldwide, especially in Western societies. Over a year, the prevalence of general sleep disturbance is estimated at around 85%, and a diagnosis of primary insomnia is estimated to be approximately 10%.9
Insomnia is associated with reduced hippocampal volume, daytime cortical gamma-aminobutyric acid (GABA) levels and activation of the caudate nucleus. In several parts of the brain, such as the hippocampus or the prefrontal cortex, inhibition of the usual decline in activity that occurs during the transition from waking to sleep has been observed. Thus, general overactivity of the arousal, emotion regulation, and cognitive systems probably leads to the pathophysiology of insomnia. For the treatment of this disease, there are effective drugs such as benzodiazepines or benzodiazepine receptor agonists. However, the use of these sleep medications is limited by their tolerance and the increased risk of addiction, morbidity and mortality with long-term use.10 In this context, the search for safe and effective compounds without adverse effects is essential.
The extent to which sleep is causally related to mental health is unclear
The aim of the 2006 study was to to trace the consequences of insufficient sleep in terms of chronic sleep reduction, rather than acute sleep deprivation on fatigue, mood, cognitive performance self-estimation, and daytime sleepiness in different age-social groups. The age group of the subjects reflected their social situation and the organization of working hours: adolescents followed strict school schedules with starting times often before 8:00 h; university students had more flexible timetables; young employees were engaged in regular morning schedules or irregular daytime hours or day or night shifts.3
The most frequent complaints of adolescents included tiredness on awakening (46%), nervousness and general weakness. University students reported excessive sleepiness (50%), tension and nervousness. Employees suffered the most from negative moods, such as tension (49%), nervousness and irritability. The findings of the study show that chronic sleep loss seems to affect women more than men. The correlation of fatigue and mood with the need for sleep and the sleep index was more pronounced in younger subjects.
Surprisingly, symptoms of fatigue in school children and students were just as common as in hard-working adults. Since the problem of insufficient amount of sleep is already present among young people, it is necessary to pay more attention to the organization of their working time.3
One way to test the causal link of sleep quality to mental health is to evaluate the extent to which interventions that improve sleep quality also improve mental health. A meta-analysis of randomized controlled trials was conducted, which reported the effects of an intervention that improved sleep on complex mental health and on seven specific mental health problems. 65 trials with 72 interventions and 8,608 participants were included in the meta-analysis.
Sleep improvement led to a moderately significant effect on overall mental health, depression, anxiety, and rumination, followed by a small-to-moderately significant effect on stress, and finally a small-significant effect on positive symptoms in psychosis. A cause-and-effect relationship was also clarified, in the sense that greater improvements in sleep quality led to greater improvements in mental health. These findings suggest that sleep quality is causally related to psychological difficulties. Future research might consider how methods that improve sleep quality could be incorporated into services to improve mental health. We should also study the mechanisms that affect mental health by influencing the quality of sleep.4
Problems with sleep are common. A review of several hundred epidemiological studies concluded that nearly one-third of the general population has symptoms of insomnia (defined as difficulty falling asleep and/or staying asleep), between 4% and 26% experience excessive sleepiness, and between 2% and 4% of people experience obstructive sleep apnea.5 Additionally, a recent study with more than 2,000 participants reported that the prevalence of “general sleep disturbances” was 32%. It was previously assumed that mental health difficulties lead to sleep problems, however the reverse may also be true, such that poor sleep contributes to the onset, recurrence, and maintenance of mental health difficulties.
Sleep disorders and stress have been in the top 3 consumer health concerns in recent years.12 According to the Centers for Disease Control and Prevention (CDC), 24 hours of sleep deprivation is equivalent to a blood alcohol concentration of 0.10%. Such a 24-hour lack of sleep can cause numerous symptoms.
Taking into account everything that has been stated so far, there is a clear need to find other ways to contribute to the quality and duration of sleep, in addition to classical drug therapy, which has longterm unwanted effects. In addition to adjusting the diet and introducing bedtime routines, dietary supplements play a key role. We will discuss several ingredients below, as they have shown a positive effect on sleep in studies and in practice.
Melatonin
Melatonin is a neurohormone secreted by the pineal gland in the brain, and is well known for causing and regulating sleep. Light suppresses melatonin synthesis. The primary use of melatonin as a dietary supplement is to normalize abnormal sleep patterns.
Melatonin may also have general neuroprotective effects related to its antioxidant effects.
There are some demographic groups that tend to have irregular melatonin production in their body. Smokers tend to be less responsive to supplementation, and older people tend to not produce as much during night time. Depression has also been associated with lower melatonin levels.
Very rarely, serious adverse effects resulting from melatonin supplementation (often in very high doses) have been reported. Taking melatonin is not associated with negative feedback (when taking a supplement causes your body to produce less of the hormone). It is also not addictive. Melatonin’s primary mechanism is by helping decrease the time it takes to fall asleep (as a hormone, that’s its primary job). Doses between 500 mcg (0.5 mg) and 5 mg of melatonin appear to be effective in regulating the sleep cycle. It is recommended to start with 500 mcg, then increase the dose to 1 mg if necessary. Higher doses belong to the drug category and should be taken under the supervision of a doctor. The benefits of melatonin are not dose-dependent, as taking more will not help to fall asleep faster.
For help to fall asleep, it is recommended to take melatonin approximately 30 minutes before bedtime. As part of the study to determine the optimal dose of melatonin, research was conducted on children. It showed that their treatment compared to the general Dutch population14 can be sustained over a long period of time without significant deviation in development, regarding sleep quality, puberty development and mental health scores.
In a multicenter, randomized, placebo-controlled study of 170 ambulatory patients aged 55 years or older, who suffered from primary insomnia, the effects of 2 mg prolonged-release melatonin (PR-melatonin) for 3 weeks were evaluated compared to placebo treatment. It was the first drug shown to significantly improve sleep quality and morning alertness in these patients, suggesting restorative sleep. Also, the patients did not have withdrawal symptoms after discontinuation.15 We emphasize the fact that melatonin in that study belonged to the category of drugs due to the high dose contained.
Here is another study that was conducted to systematically review the effect of melatonin on sleep quality. Evidence from randomized clinical trials (RCTs) investigating the effects of melatonin on sleep quality as assessed by the Pittsburgh Sleep Quality Indeks (PSQI) in adults with various diseases is summarized. According to this index, it was determined that treatment with exogenous melatonin has positive effects on the quality of sleep in adults.7
In order to overcome the short-term effect of melatonin on easier falling asleep and to prevent late night awakenings, some manufacturers have developed a unique form of micronized melatonin that enables both immediate and prolonged release, thus comprehensively improving the quality of sleep.
In most European countries where melatonin is allowed as an ingredient in food supplements (including Croatia), the maximum dose is 1 mg per day. It is different in Turkey, where the content of melatonin is allowed up to 3 mg for adults, but with a mandatory warning on the declaration:”It should not be used by pregnant or breastfeeding women and persons under 18 years of age”, “Do not drive, operate machinery or consume alcohol while using this product”, “It should not be used for more than two months”. Germany, Ireland, Iceland and Slovenia do not allow melatonin in food supplements, but classify it as a drug, regardless of dosage.
Saffron, Crocus sativus L.
The saffron extract used in food supplements is among the most expensive extracts, just as the spice used in food preparation is among the most expensive spices. But there is a valid reason for that.
Saffron belongs to the iris family. Its threads located in the center of the purple flower are stigmas. There are only three orange-yellow stigmas in each flower, which means that it takes many flowers to produce a small amount of extract or spice. Each kilogram of saffron contains between 15 and 20 thousand stigmas. If you were to grow saffron yourself, you would need 75 thousand flowers to get half a kilogram.
But that is not the only reason why saffron is so expensive. Saffron flowers are very delicate, and the only way to properly remove the threads is to tear them off by hand. The flower is so delicate that if the saffron threads are not harvested soon after the flowers bloom, they will wilt and become unusable. It takes about 370 to 470 hours of work to harvest one kilogram of saffron. However, if we consider that sleep and the quality of sleep are of inestimable importance for human health, then the price of saffron extract is a justified investment.
The dried stigmas of the saffron plant used in traditional medicine, and the compounds it contains – safranal, crocin and crocetin – have been largely studied for their effects on depression and anxiety in humans.5 Additionally, saffron appears to have beneficial effects on sleep duration and quality, as evidenced by previous reports using different approaches and protocols. Some studies used a whole saffron extract, while others examined the effects of its active compound crocetin.
It is undeniable that saffron extract is effective in the context of depression and anxiety, but its effect on sleep quality has not been investigated by objective approaches until recently. For this purpose, a randomized, double-blind, placebo controlled study was conducted in subjects presenting mild to moderate sleep disorder associated with anxiety. Sixty-six subjects were randomized and supplemented with a placebo (maltodextrin) or a saffron extract (15.5 mg per day) for 6 weeks.8
Saffron extract intake was associated with improvements in sleep quality in adults with self-reported sleep complaints. Further studies using larger samples sizes, treatment periods, objective outcome measures, and volunteers with varying demographic and psychographic characteristics are required to replicate and extend these findings.16
In conclusion, the above studies provide evidence that saffron extract could be an interesting natural and safe strategy to improve sleep duration and quality of sleep on population presented mild to moderate chronic primary sleep disorder.
Biopeptides from milk
Developed in France, Lactium is the generic name of bioactive milk-derived peptides. They are amino acid chains concentrated from casein, derived from cow milk, that act on GABA receptors.
However, its discovery was ultimately thanks to babies. The enzymes present in babies’ digestive systems are responsible for the release of this bioactive peptide resulting in a state of bliss. The digestive enzyme system of adults is no longer capable of releasing this ioactive milk peptide. After many years of work, researchers have developed an innovative process to reproduce a baby’s digestive system. They used the well-known digestive enzyme trypsin to isolate a milk protein hydrolyzate containing the bioactive peptide alpha-casozepine from casein.
Lactium® improves sleep, reduces stress and cortisol levels while inducing relaxation and improving mental function. (Clare & Swaisgood, 2000; Delini-Stula & Holsboer-Trachsler, 2009; de Saint-Hilaire, Messaoudi, Desor, & Kobayashi, 2009). It is an effective alternative to medication for anxiety and insomnia.
The study evaluated the effects of alpha-s1 casein hydrolyzate (ACH) on the subjective and objective sleep profiles in subjects with poor sleep quality. A double-blind, randomized, cross-over trial was conducted with 48 participants (49.0 ± 1.7 years, 65% female) who exhibited a mild to moderate degree of sleep disturbance. During the first four weeks, they
received either ACH or placebo, and the counterpart was administered in precisely the same way after a four-week washout period. Findings suggest that refined ACH is well tolerated and may improve sleep quality, with possible cumulative beneficial effects with long-term administration.17
Lactium® can be used as an ingredient in a wide range of products, in capsules, tablets, powders, chewing gums, drinks, as an stand alone active substance or in combination with other ingredients.
Magnesium
Magnesium is found in many food supplements as an independent ingredient, or in combination with other active ingredients for numerous purposes. It is often found in food supplements that are intended to promote healthy sleep. The reason for this is justified. Namely, magnesium plays a role in supporting deep, restorative sleep by maintaining healthy levels of GABA, the neurotransmitter that promotes sleep. Research shows that supplemental magnesium intake can improve sleep quality, especially in people with poor sleep.
There are many other ingredients that offer promising results in improving sleep quality. One of them is DailyZz by Kemin, a clinically tested combination of ingredients for natural sleep support. Clinical dana supported by rigorous testing of 100 healthy participants with occasional sleep problems showed that the ingredient can help improve sleep quality, support healthy sleep and improve an individual’s functioning during the following day.
One of the interesting new findings is that sleep fragmentation and short sleep duration are associated with intestinal dysbiosis, a fact that will surely gain importance in the future. It was also found that the addition of probiotics improves the subjective quality of sleep. The quality and duration of sleep can be an important goal for maintaining a healthy gut microbiota composition, but the cyclical nature of this relationship should not be overlooked.18
References:
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12 Euromonitor survey, 2021
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