QUALIA NIGHT combines 25 ingredients used to support a broad array of processes and pathways involved in relaxation, sleep, stress resilience, cognition, rejuvenation, and immunity.*
NOTABLE STUDIES
These are a few publications from scientific journals highlighting our Qualia Night ingredients.
A study found in the National Institutes of Health (Pubmed 32021735) reported that Ashwagandha supports sleep quality and a healthier stress response.*
A study found in the National Institutes of Health (Pubmed 469515) reported that a low dose of L-Tryptophan supports deep sleep.*
A study found in the National Institutes of Health (Pubmed 26571987) reported that Holy Basil (Ocimum sanctum) supports cognition and mood.*
A study found in the National Institutes of Health (Pubmed 18191355) reported that Gotu Kola (Centella asiatica) supports calmness.*
A study found in the National Institutes of Health (Pubmed 19429065) reported that Polygala tenuifolia has nootropic benefits.*
A study found in the National Institutes of Health (Pubmed 29614679) reported that the combination of sesamin (from sesame seed extract) and astaxanthin supports cognitive function.
OUR INGREDIENTS
KSM-66 Ashwagandha® (Withania somnifera) Root Extract
Ashwagandha (i.e., Indian ginseng) is a Rasayana—the category of elixirs and tonic herbs prized by the branch of Ayurvedic medicine concerned with rejuvenation, and focused on promoting a youthful state of physical and mental health. Ashwagandha holds a prominent place among the Rasayana herbs, where it was used for many reasons including as general tonic and to infuse energy and vigor in circumstances characterized by exhaustion or a lack of physical energy. As the English name Indian ginseng implies, Ashwagandha was believed to share some of the attributes of ginseng, in essence supporting multiple areas of health and well-being, especially under conditions characterized by increased stress. Herbs that produce these types of nonspecific resistance to and recovery from stress—and which typically also support general well-being, healthy energy, and homeostasis—are called adaptogens. Ashwagandha, like most Rasayana herbs, meets the criteria to be considered an adaptogen. We included KSM-66 Ashwagandha® because it supports sleep quality, relaxation, muscle recovery, cognitive function, immunity and a healthier stress response: These are the areas at the core of what Qualia Night was designed to deliver.*
Gotu Kola (Centella asiatica) Whole Herb Extract
In Ayurvedic medicine, gotu kola is considered to be a mental rejuvenator (medhya Rasayana), where it was traditionally used as a tonic herb to counter mental fatigue and improve thinking. It was thought to be particularly useful during times of increased mental demands. Modern science has upheld some of this reputation—gotu kola is a nootropic and supports brain repair and rejuvenation processes. Gotu kola also supports the GABA pathway: GABA is the brain’s chief inhibitory neurotransmitter. This means that at night GABA acts a bit like a braking system that allows the brain to shift into a state that is better suited for relaxation and sleep. We included gotu kola because, unlike many other nootropics that are best taken only at the beginning of the day, gotu kola is a great fit at the end of a busy day because it is calming and supports repair and rejuvenation processes.*
Holy Basil (Ocimum sanctum) Leaf Extract
In Ayurvedic medicine holy basil is called “tulsi,” which translates as “the Incomparable one.” It is one of a small number of herbs categorized as Rasayana, the category applied to elixirs and tonic herbs prized for rejuvenation and revitalization. It was believed to guard the body from stress of all types, while keeping the mind sharp and the body healthy. In modern times, holy basil is categorized as an adaptogen, supporting a healthy stress response. We included holy basil because one of the leading causes of poor sleep is hyperarousal—an overactive stress response and over aroused nervous system. Holy basil also supports mood, cognition and immunity. This combination makes it a perfect fit for nighttime relaxation and restoration.*
Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract
Ganoderma lucidum is considered the “mushroom of immortality” and called Reishi in Japanese—this is the name it’s most known as in America—and Lingzhi in Chinese. In Traditional Chinese Medicine, it is considered to be a shen tonic. Shen tonics were believed to play roles in supporting peace of mind, joy, emotional balance, optimism, sound sleep, and clear thinking. Reishi’s traditional uses, which included replenishing Qi, easing and centering the mind, increasing resistance to fatigue, promoting well-being, and supporting sleep, are consistent with this role as a shen tonic. It was thought to be ideal for countering restlessness and quieting an overactive mind. One reason that Reishi was included in Qualia Night was because of these traditional roles. The combination of supporting sleep (without producing sleepiness) and calming/centering the mind were particularly appealing, since a primary goal of the product was going to be focused on evening relaxation and readiness for sleep. In addition to these traditional uses, modern research on reishi mushrooms has focused on immune system support and rejuvenative processes, including stem cell function. These were other areas we wanted to support, and reasons we included Reishi.*
Schisandra chinensis Fruit Extract
The fruits of Schisandra chinensis are berries. They are one of the 50 fundamental herbs in Traditional Chinese Medicine, and have been used in traditional medicine in Japan, Korea and Russia. The berries are known for possessing all five basic flavors: salty, sweet, sour, pungent (spicy), and bitter. S. chinensis berries contain schisandra lignans—lignans are a subgroup of non-flavonoid polyphenols that interact with gut microbiota (i.e., gut-brain axis)—not found in other plants. S. chinensis fruits are often described as being an adaptogen, supporting broad resistance to stress, and enhancing mental and physical performance. S. chinensis fruits were included in Qualia Night for a few reasons. One reason is that traditionally they are used as a restorative tonic and for cognitive performance, both of which are major goals of the formula. Another reason is that in preclinical research S. chinensis fruits enhance calmness and relaxation, and support readiness for sleep. And a third reason is that they seem to be complementary with other ingredients, especially the lignans found in sesame extract (i.e., sesamins).*
Ziziphus jujuba Seed Extract
The Ziziphus jujuba plant is native to many regions in South Asia. The fruits and seeds—in research the seeds are called Ziziphus spinosa, Semen Ziziphi spinosae, or the Chinese name Suanzaoren—have been used in both Korean and Traditional Chinese Medicine (TCM) where they are believed to alleviate stress and were used to calm the mind and spirit. Because of these properties, the seeds are one of the most commonly used herbs for supporting sleep and relaxation in China and other parts of Asia. In preclinical research, compounds found in the seeds support the GABA pathway: GABA is the brain’s chief inhibitory neurotransmitter and acts a bit like a braking system that allows the brain to shift into a state that is better suited for relaxation and sleep. Unlike many European sleep herbs, which are typically taken just before bed, many of the core TCM herbs for supporting sleep were given earlier in the evening or the day (i.e., they are not known for producing feelings of sleepiness shortly after taking them). The seeds were included in Qualia Night because of their traditional use for supporting sleep and a healthy stress response, since a major goal of the product is countering evening stress and supporting sleep readiness.*
Polygala tenuifolia Root Extract
In Traditional Chinese Medicine, Polygala tenuifolia root is one of the most used herbs to support the brain and central nervous system. Traditionally it was often used to reduce forgetfulness and support brain performance during aging (i.e., it’s what we’d consider a nootropic today). Preclinical research suggests it supports brain protection and repair processes and molecules (such as BDNF and NGF), counters stress, supports sleep, and influences both adenosine signaling—a molecule involved in the sleep homeostatic drive—and GABA signaling—a neurotransmitter involved with relaxation at night and sleep. It’s a fit in Qualia Night because it supports these signaling pathways, without producing sleepiness at the doses used. It’s also a fit because it may support a healthier response to stress—one of the leading causes of poor sleep is an overactive stress response and over aroused nervous system (i.e., hyperarousal).*
White Peony (Paeonia lactiflora) Root Extract
The roots of white peony are one of the most common herbs used in Traditional Chinese Medicine (TCM), where some of its uses included supporting emotional stability, mental focus, and immunity. It is one of the four herbs in a TCM herbal formula called Si Ni San, which is used to support sleep quality and help with mental fatigue. White peony root contains a compound called paeoniflorin that influences adenosine signaling—a molecule involved in the sleep homeostatic drive. Preclinical research has also reported that paeoniflorin supports brain protection and repair processes and molecules (such as BDNF and NGF), counters stress, influences learning, and promotes a balanced mood. An extract standardized for paeoniflorin was included in Qualia Night because of this combination of potential for brain rejuvenation, nootropic, anti-stress, and sleep supportive functions.*
Hawthorn Leaf and Flower Extract
The leaf and flowers of Hawthorn—Crataegus sp. such as C. monogyna and C. oxyacantha—was a heart tonic (i.e., something intended to make the heart function more efficiently) in European herbal traditions. Other traditional uses include when extra support was desired for stress, nervousness and sleep. Interesting aspects of hawthorn lore are comments in herbal texts related to removing a hurried feeling, having a calming effect on the nerves and the heart, and being a mood brightener. In other words, hawthorn was used to support the heart both physically and emotionally. In Celtic Lore, hawthorn was believed to have the power to put people to sleep. Hawthorn research has focused primarily on the cardiovascular system and supports hawthorn having restorative benefits when taken over time. While not nearly as researched for relaxation, mood and sleep, available research, mostly done in animals. has been supportive of these traditional uses. It was included in Qualia Night because we wanted to include support for heart rejuvenation, and using an herb that has a reputation for calming and sleep supportive properties made it a perfect fit.*
Saffron is a spice derived from the flowers of Crocus sativus. It’s been used and traded as a spice for at least 4000 years and is considered the world's most costly spice by weight. While saffron had a wide range and long list of traditional uses, several of them overlap with what we were trying to accomplish. As an example, in Traditional Iranian Medicine saffron was thought to be useful for supporting sleep and mood, and to be a heart tonic. And in India it was used as a nerve and heart tonic, and for relaxation and sleep support. Saffron is a source of crocin (responsible for saffron's color), picrocrocin (a bitter compound giving the characteristic taste), and safranal (gives part of the fragrance) as well as the macular (eye) carotenoids zeaxanthin and lycopene These compounds have each been the subject of research on their own. And there’s been a growing body of research in the use of saffron for health, including in areas that overlap with some traditional uses such as mood, cognition, vision, and more recently sleep. We felt saffron would be a fit in Qualia Night because of this combination of sleep support, mood enhancement, and relaxation.*
Vineatrol®20 Grapevine Extract
Vineatrol®20 is a Vitis vinifera (i.e., the common grapevine) extract cultivated in France. It’s standardized for three things: (1) trans-resveratrol >5%; (2) trans-ε-viniferin >5%; and (3) total resveratrol monomers and oligomers >20% (hence the 20 in the name). Trans-resveratrol is an example of a resveratrol monomer—a monomer is a molecule that can be bonded to other identical molecules—so think of it as one unit of resveratrol. Trans-ε-viniferin is a resveratrol dimer, which means it’s two identical resveratrol molecules bound together into an oligomer: Think of it as two units of resveratrol. But there’s quite a few other resveratrol derivatives in the resveratrol oligomer family, since up to eight resveratrol molecules can couple together. While trans-resveratrol is the most studied of the resveratrol derivative family, some of the other resveratrol derivatives may have structure/function benefits not shared by trans-resveratrol, could be more potent than trans-resveratrol for certain functions, and tend to be complementary when given together. In other words, there’s a synergy in the mix of resveratrol derivatives that naturally occur in the grape plant. Resveratrol is best known as a calorie restriction mimetic (i.e., supports healthy aging functions), and for supporting metabolism, heart health, immunity, and cognition. But why was resveratrol in general, and Vineatrol®20 specifically, included in Qualia Night? During our research on the homeostatic sleep drive, we discovered preclinical and animal studies indicating that resveratrol interacts with this system. We also found mentions of low doses of resveratrol benefiting sleep quality and next day feelings of being refreshed in news articles. This information was based on unpublished data that we were able to track down. It turned out that resveratrol wasn’t what was used: It was Vineatrol®20, so it’s what we sourced and included.*
Olivex® Olive Fruit Extract
Olivex® is an olive fruit extract made from French olives, with about 380 pounds of olives needed to make 1 pound of the extract. This concentration is needed to create an olive fruit extract standardized for the olive polyphenols hydroxytyrosol and tyrosol. Although olive oil polyphenols are present in low amounts in olive oil, they seem to be of great importance when it comes to the health benefits. Olive polyphenols have been receiving attention for heart and brain health, as well as healthy aging. It was animal research in the brain health area that caught our initial attention. Although we are inactive during sleep, the brain and body are not; they continue to do metabolic work around the clock. ATP is a critical molecule for cellular work, and it’s a molecule that is interwoven with sleep cycles. Adenosine—the “A” in ATP—is believed to be the key molecule in the homeostatic sleep drive. And in several brain regions there’s a surge of ATP during the initial hours of sleep. This ATP surge appears to be especially important for deep sleep. In general, the ability to make ATP is diminished with aging. Could one of the reasons that sleep becomes more of an issue during older age be related to this decreased ability for the brain to have an ATP surge? In searching for answers and ingredients that might support brain ATP, we came upon a mouse study where olive polyphenols restored brain levels of ATP in old mice to be similar to levels found in young mice. This doesn’t mean it would do this in humans, but it was interesting. What sold us on olive polyphenols, and Olivex® specifically, was a result of looking into resveratrol. We found mentions of low doses of resveratrol for benefiting sleep quality. When we tracked down this data, we discovered the scientists didn’t only investigate resveratrol; they also gave both animals and humans an extract with olive polyphenols and monitored sleep. You’ve probably guessed: The extract was Olivex®. In the data, either Olivex® or Vineatrol®20 were given. Both supported sleep. Rather than choose one or the other, we decided to include both based on research that is suggesting they may have additive functional benefits, which makes sense given the central role both play in Mediterranean diets.*
Wild Blueberry Fruit Extract
Wild blueberries (Vaccinium angustifolium) are native to North America and are both smaller and have more intense color than cultivated blueberries. They also have higher anthocyanin and polyphenols content, which are the phytochemical compounds that are thought to be largely responsible for why blueberries support cognitive function. Blueberry polyphenols also act as food, of sorts, for the gut microbiota, so support the gut-brain axis. Since a primary goal of Qualia Night is to support long-term brain health, wild blueberries were a fit. Blueberries have also been found to support healthy stem cell activity in animal studies, which fits with a goal of including ingredients that support rejuvenation functions. The European cousin of wild blueberries is called bilberry. One of its traditional uses was supporting both vision and night vision. Most of the vision research has been on these European cousins, but North American blueberries have produced functional dark vision responses in the one study where it was tested. And, after all, seeing at night is an important part of night time function. The last reason that we included a wild blueberry extract is because we like ingredients that have additive and synergistic actions. In some cognitive studies, blueberry and grape extracts have been complementary, so included both.*
Sesame Seed Extract
Sesame (Sesamum indicum) seeds are one of the two best food sources of lignans. Lignans are a category of polyphenols, and like other polyphenols are broadly described as antioxidants. Lignans tend to be metabolized by the gut microflora. During this process both the lignans and gut microflora are changed. As a general rule of thumb, lignans shape the populations of gut microbiota, and as a result, may influence the gut-brain axis. Sesame seeds are also a source for tocopherols and tocotrienols, the class of compounds with vitamin E activity. Sesame lignans, both individually and in combination, influence a range of biological functions. While sesame seeds have about 16 different lignans, the one that has received the most research is sesamin. In animal studies, sesamin has been neuroprotective and supports molecules like BDNF, which is involved in nervous system repair and growth. It has also countered changes in behavior caused by stress, and positively influenced both cardiovascular and liver health. Some of these findings have been replicated in human studies. As an example, sesamin has been reported to support cardiovascular health. Several human studies on sesamin have combined it with other ingredients. Sesamin and astaxanthin have supported cognitive function and recovery from mental fatigue. Sesamin and Schisandra chinensis—another source of lignans—support liver health and blood fluidity. Qualia Night included a sesame seed extract because the product’s goals included a focus on nootropics (but ones which are not stimulating so are fits in the evening), the gut-brain axis, and repair functions and molecules like BDNF. We also like to include ingredients that stack well together. So it’s not a coincidence that Qualia Night has sesamin, astaxanthin, and schisandra.*
Note: The sesame extract we use is standardized for sesamin content.
γ-Oryzanol
Gamma-oryzanol (γ-oryzanol) is a mixture of lipid molecules called steryl ferulates. Like many secondary metabolites in plants, and similar to tocopherols which also naturally occur in the oils of seeds, γ-oryzanol is considered to be an antioxidant. The best food source is rice bran and germ—γ-oryzanol gets its name from the botanical name for rice, Oryza sativa. In parts of the world where rice bran oil is used or rice bran is consumed, it is a naturally occurring part of the diet; however, there would be a negligible amount found in a typical western diet. It has been sold in Japan since 1962, and most of the human studies on it have been done in Japan and published in non-English papers. These studies have focused primarily on supporting aspects of menopause, mood, nervous system, and heart health. Very modest amounts of γ-oryzanol—10 to 50 mg a day—have been needed to produce a functional benefit in some of these studies. Animal studies have suggested cognitive, mood, stress, immune, and sleep support functions. Our interest in including it in Qualia Night was largely driven off these latter functions, and particularly animal research that suggested its sleep supportive actions might be related to histamine signaling. Circadian changes in histamine neurotransmission play an important role in sleep-wake cycles and both daytime and night time performance. Histamine neurons fire rapidly during periods of wakefulness, more slowly during periods of relaxation/tiredness, and stop firing altogether during REM and NREM sleep. Compounds in rice bran oil, including γ-oryzanol, appear to support this system, though so far this research has entirely been done in animals. While not a driver for inclusion, we liked the idea of augmenting the intake of an ingredient that’s not found in a meaningful amount in many people’s diets.*
AstaPure® Haematococcus pluvialis microalgae extract (3% astaxanthin)
Astaxanthin is one member in a class of natural pigments called carotenoids—carotenoids are fat-soluble yellow, orange, or red pigments. Astaxanthin is on the reddish end of the carotenoid pigment color continuum and is produced by some freshwater and marine algae and microorganisms. It is the pigment that gives salmon and crustaceans (i.e. shrimp, crab, lobster, and crayfish) an orange-red color, and flamingos their characteristic pink coloration. These organisms, like humans, are unable to make the astaxanthin themselves; they consume it in the aquatic food chain. The most concentrated source of astaxanthin is a microalgae called Haematococcus pluvialis. Astaxanthin is a plant defense compound, in other words, more of it is made when the environment is stressful to protect a microalgae like H. pluvialis from, for example, intense UV radiation from sunlight. Since it is fat-soluble, astaxanthin is active in places with high lipid content, where it’s a powerful antioxidant. These places include cell membranes (which have a lipid bilayer), mitochondria, and the brain and nervous system. One of the things that make astaxanthin fairly unique, even compared to other carotenoids, is that its unique shape allows it to stabilize and protect lipid membranes. Astaxanthin can cross the blood-brain barrier (BBB), and accumulates in the brain over time. Even low amounts, as long as they are in the diet consistently, can help support healthy cellular membranes. We included astaxanthin in Qualia Night because of the growing body of research on cognitive function support, as well as protective, repair and regenerative processes in the brain. Other reasons we included astaxanthin included immune support and gut-brain axis. We also like to include ingredients that are complementary. Astaxanthin and sesamin—found in sesame seed extract—have supported cognitive function and recovery from mental fatigue, so both are included in Qualia Night.*
Lycopene
Lycopene is one member in a class of natural pigments called carotenoids—carotenoids are fat-soluble yellow, orange, or red pigments. Lycopene is on the red end of the carotenoid pigment color continuum. The main dietary source is red tomatoes and tomato products—over 80% of the lycopene in American diets comes from tomato products—but lycopene can be found in lower amounts in some other pink-red colored foods such as watermelon and grapefruit. Lycopene is a plant defense compound, acting to protect tomatoes, as an example, against environmental stress such as sunlight. Since it is fat-soluble, lycopene is active in places with high lipid content, where it’s a powerful antioxidant. These places include cell membranes (which have a lipid bilayer), mitochondria, and the brain and nervous system. We included lycopene in Qualia Night because of a growing body of research, mostly in animals, suggesting support of protective, repair and regenerative processes in the brain. Some animal research also suggests it might support the gut-brain axis and play a functional role in normalizing GABA levels, a neurotransmitter involved with relaxation at night and sleep, under some circumstances.*
L-Tryptophan
L-tryptophan is an essential amino acid. This means the body cannot synthesize it: it must be obtained from the diet. It’s been known for decades that L-tryptophan has niacin equivalent activity in the body (i.e., we can make the NAD+ molecules from it). L-tryptophan is unique because it’s the only way to build NAD+ that doesn’t start from one of the older or newer vitamin B3’s. L-tryptophan does this by a de novo synthesis pathway, which creates a niacin molecule through a series of biological reactions (many other important molecules are also created in this process). In the morning, most L-tryptophan—as much as 95%—is used in this pathway. During the night, while the body might be inactive, our cells are not. They just change the jobs that are prioritized. This means they still need NAD+, and the things it supports like building ATP, activating cellular defenses, and repairing DNA (this last job appears to increase at night). At night the priorities for L-tryptophan also shift a bit. While most of it’s still funneled into the de novo pathway, the amount that gets directed to a different pathway, 5-hydroxytryptophan (5-HTP) → serotonin → melatonin, goes up at night. This is important because this alternate pathway is critical for regulating sleep-wake cycles and nighttime body clock functions. Because of this pathway, and it’s role as a building block for melatonin, L-tryptophan has been studied for and used to support healthier sleep. And, while high doses are often used, in a study that compared different dose amounts, a low dose performed the best. The explanation for this might be that L-tryptophan is not something that we get huge amounts of in the diet, so even a low dose can augment dietary intake enough to essentially fill the tanks. So a key thing to remember with L-tryptophan, and it can apply to lots of ingredients used in dietary supplements, is that more may not be better. One option for supporting the melatonin synthesis pathway is to give 5-HTP instead of L-tryptophan. The drawback in choosing that option is it removes optionality. 5-HTP is committed to the melatonin pathway, while L-tryptophan can be used to make a variety of brain-important compounds in addition to those made in the melatonin pathway. In principle, we think it is better to ensure the brain has adequate tryptophan resources, and allow it to decide how to best use them. This is especially important to us in products intended to be used by a broad range of adults (while 5-HTP might be more appropriate for a very small subset of the population with genetic polymorphisms in the enzyme that makes it). The other benefit of having L-tryptophan in an evening relaxation formulation is that low-to-moderate doses of L-tryptophan support skills that fall into the social cognitive domain: these include prosocial behaviors like cooperation, empathy, getting along with others, and altruism. The evening is a perfect time to have these behaviors step to the forefront.*
L-Theanine
L-theanine is a calming amino acid that naturally occurs in green tea. It is routinely used in nootropic stacks, because it promotes focused attention and mental alertness, but does it in a way that supports a calm, relaxed sense of mental energy. L-theanine promotes alpha brain waves (α-waves), which are thought of as a marker of relaxation. This brain state also reduces the perception of stress, which is important in the evening since stress can be a cause of poor sleep in some people. Collectively, these attributes—calming, relaxing, anti-stress—make L-theanine a fit for a formula like Qualia Night that is intended to enhance feelings of relaxation at night, help with feelings of stress, and support sound sleep. L-theanine has a few other lesser known functional actions that also make it a fit. L-theanine can be broken down into glutamate, which is a building block for glutamatergic signaling (i.e., the glutamate-GABA pathway) and for glutathione, an antioxidant used in every cell for defenses and detoxification. And L-theanine, because of another metabolite, primes specialized immune cells—gamma delta T cells—that help the immune system respond more efficiently to new antigens and have enhanced immune memory. And L-theanine interacts with cells in innate and adaptive immunity, supporting general immune health. GABA signaling, antioxidant defenses, detoxification, and immunity are all jobs that still occur at night. We might not be active in the middle of the night but our cells are.*
Betaine, also called trimethylglycine (TMG), was originally found in sugar beets (Beta vulgaris), which is the source of its name. Betaine is an important cofactor in methylation, a process that occurs in cells where methyl groups (-CH3) are donated for other processes in the body. Both making melatonin, our darkness hormone, and serotonin require methylation. Betaine has largely been used to support liver and heart health, with a prominent role in normalizing homocysteine metabolism—betaine is thought to be the source of up to 60% of the methyl groups required for the methylation of homocysteine. Newer research suggests betaine is an inhibitory neurotransmitter—neurons have betaine/GABA transporters. And there is increasing data to suggest that betaine may support cognition and neuroprotection. These suggest it could be a fit in a product targeting relaxation, sleep, and brain performance. One of the steps we take when developing new formulas is to look for reports from self-experimenters (i.e., N of 1 data). We do this to see what individuals are reporting and to check whether their experiences match what’s reported in research. In the case of betaine, we found something in our N of 1 search that hasn’t been shown in research yet. While we couldn’t find any studies, animal or human, on betaine for supporting sleep, we found a number of comments on sleep from people who had added betaine into their night time routines. This led us to experimenting with adding some into the formula as we developed Qualia Night.*
Uridine (as Uridine-5'-monophosphoric acid disodium salt)
Uridine is one of the 5 standard nucleosides; the others are adenosine, thymidine, cytidine and guanosine. These compounds are the building blocks of DNA and RNA, and play a central role in cellular metabolism. ATP—the “A” standing for adenosine—is known for its role in carrying packets of chemical energy needed for cellular functions, but UTP (made from uridine instead of adenosine) is also an activator of substrates in some specific metabolic reactions. Uridine can be used to support the Kennedy pathway, which is involved in making the phospholipids needed for healthy cell membranes throughout the body and in the brain. And it may support different neuroregulatory processes and neurotransmitters. These structural and functional roles have led to it being used as a nootropic. We included it in Qualia Night for these nootropic structure/function reasons, and because uridine is considered to be one of the natural sleep-promoting substances. In several chrononutrition studies (i.e., research that focuses on timing), uridine has been one of a few nutrients used to augment night time infant formulas. We use a phosphorylated form of uridine because it is stable and this helps it get past the digestive system and liver intact.*
Grapefruit Whole Fruit Extract
Grapefruit is a citrus fruit that is rich in antioxidants, including bioflavonoids such as naringin. It’s naringin that gives grapefruit its distinctly bitter taste. Naringin, like all flavonoids, is part of a larger group of plant compounds called polyphenols. We included a grapefruit extract standardized for naringin in this formula because of some preclinical research suggesting that it may support enzymes in both adenosine—a key molecule in the sleep homeostatic drive—and GABA metabolic pathways. One of our formulation goals is to support entire pathways. This means, among other things, identifying enzymes in the pathway that are important in ensuring the flow of molecules through the pathway. We then look for compounds that may have an ability to support these enzymes. This research led us to naringin, which in preclinical studies, in other words, in studies in cell cultures and animals, supported key enzymes we were concerned about. But we only included a very low amount of naringin—about what would be found in ⅓ of an ounce of grapefruit juice—because we did not want to substantially influence the activity of the cytochrome P450 enzymes that naringin may influence. Another goal in our formulation strategy is to include more than one ingredient that may serve the same purpose, which allows us to include lower amounts of an ingredient. Quercetin, as an example, is also included, and supports several of the same enzymes as naringin.*
Quercetin (as Quercetin dihydrate)
Quercetin is a plant flavonol, which is one of the polyphenol categories. Polyphenols play important roles in the plant kingdom. One of these roles is protecting plants from environmental stress such as pests and UV irradiation from the sun. Because of this role, they tend to concentrate in parts of the plant that come into more contact with the outside world. Quercetin is an example. Red onions are one of the better food sources of quercetin. But the quercetin isn’t uniformly spread through red onions; it concentrates in the outer skins (which are usually thrown away when onions are peeled before use) and the part closest to the root. It’s useful to think of polyphenols as being somewhat akin to recommendations to eat a variety of fruits and vegetables: It's prudent to consume a variety of polyphenol compounds (rather than just one or several in very high amounts) because they tend to have complementary interactions. This is one reason that many of the ingredients we included in Qualia Night are standardized for unique polyphenols. We included a small amount of quercetin to augment the dietary intake. And we selected quercetin for this formula because of some preclinical research suggesting that it may support enzymes in both adenosine—a key molecule in the sleep homeostatic drive—and GABA pathways.*
Magnesium (as 400 mg magnesium glycinate)
Magnesium is used in more than 300 enzymes, including reactions in the GABA, an important relaxation neurotransmitter, and melatonin, the darkness hormone, signaling processes. Magnesium also plays a role in circadian rhythms, which are essential for healthy sleep-wake cycles. And it is needed for ATP to do its job—ATP is complexed with magnesium in enzyme reactions. We tend to think of energy in terms of how we feel (i.e., mental and physical energy) and associate it as being something we need during the day. But ATP is a chemical energy carrier. And cells in the brain and body continue to work at night, requiring chemical energy, even if we are inactive (i.e., asleep). In fact, in several brain regions there’s a surge of ATP during the initial hours of sleep. This ATP surge appears to be especially important for deep sleep. With known functional roles in relaxation (via GABA), sleep (via melatonin), and ATP, it’s probably not a surprise that magnesium is found frequently in dietary supplements used for sleep support, and has been given in human studies for sleep. We choose to use a glycinate form of magnesium, because this form is often thought of as being the best choice for sleep support. Glycine is not just an inert substance used to stabilize the magnesium. Glycine is a conditional amino acid, and like GABA, a molecule that acts as an inhibitory neurotransmitter. Glycine, albeit in amounts greater than found in Qualia Night, has been reported to support sleep quality and morning energy the next day.*
Vitamin B6 (as pyridoxal 5'-phosphate)
Pyridoxal 5'-phosphate (P5P) is the active form of vitamin B6. The P5P form is the bioactive form of vitamin B6: it requires less metabolic “work” to be used as coenzyme in vitamin B6-dependent enzyme reactions. P5P is included in this formula because it’s needed in the brain pathways that produce three important nighttime molecules—GABA, melatonin, and serotonin.*
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