Valerian is a medicinal herb native to North America, Asia and Europe. The root of Valerian has been used since the late sixteenth century.¹ It is used in Traditional Western Herbal Medicine, mainly to treat insomnia especially where this is associated with “nervous conditions.” Valerian is also used for anxiety, generalized pain, headache, and irritable bowel syndrome. It is listed as an approved herb in the German Commission E monographs.

Constituents & Mechanisms of Action

Valerian contains a number of plant chemicals, including:²

• Valeric acid, a terpene of the volatile oil
• Iridoids
• Alkaloids
• Lignans
• Free amino acids including:
  • GABA
  • Tyrosine
  • Arginine
  • Glutamine

It is thought that the terpenes are responsible for the effects of Valerian. However, it is more likely that the active constituents work together to produce the anxiolytic and hypnotic effects of Valerian. While the full mechanisms are still being worked out, Valerian seems to increase the concentration of GABA in the brain³ and by modulating the GABA-A receptors in the brain producing a sense of calm and improving sleep.⁴

Efficacy

Valerian root has been shown to be effective in improving:

• Sleep⁵
• Hot flushes in menopausal women⁶
• Anxiety⁷
• Response to stress⁸

Safety

According to researchers, Valerian is safer than pharmaceutical hypnotics, such as Diazepam, while improving sleep quality.⁹

References

1. Plushner, S.L. Valerian: Valeriana officinalis. Am J Health Syst Pharm 57, 328, 333, 335 (2000).
2. Hadley, S. & Petry, J.J. Valerian. Am Fam Physician 67, 1755-1758 (2003).
3. Kim, J., et al. Natural Products from Single Plants as Sleep Aids: A Systematic Review. Journal of medicinal food 21, 433-444 (2018).
4. Savage, K., Firth, J., Stough, C. & Sarris, J. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32, 3-18 (2018).
5. Bent, S., Padula, A., Moore, D., Patterson, M. & Mehling, W. Valerian for sleep: a systematic review and meta-analysis. Am J Med 119, 1005-1012 (2006).
6. Jenabi, E., Shobeiri, F., Hazavehei, S.M.M. & Roshanaei, G. The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial. Women & health 58, 297-304 (2018).
7. Kohnen, R. & Oswald, W.D. The effects of valerian, propranolol, and their combination on activation, performance, and mood of healthy volunteers under social stress conditions. Pharmacopsychiatry 21, 447-448 (1988).
8. Cropley, M., Cave, Z., Ellis, J. & Middleton, R.W. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother Res 16, 23-27 (2002).
9. Kelber, O., Nieber, K. & Kraft, K. Valerian: no evidence for clinically relevant interactions. Evid Based Complement Alternat Med 2014, 879396 (2014).

Known as Lingzhi in China and Reishi in Japan, Ganoderma lucidum has a history in Asian Medicine for promoting general health and longevity for over 2000 years.¹ “The name Lingzhi represents a combination of spiritual potency and essence of immortality and is regarded as the “herb of spiritual potency,” symbolizing success, well-being, divine power, and longevity”.²

Constituents & Mechanisms of Action

While Reishi has been used traditionally for centuries, it is only recently that researchers have started to elucidate the bioactives and their mechanisms of action in the body. The bioactive constituents include terpenes, fatty acids and sterols. Reishi displays immune and cognitive enhancing effects as well as cardioprotective, anti-cancer, and anti-depressant actions, among other effects.¹ The mechanism for its action in sleep is not fully known but is thought to involve TNF-α³ as well as the GABA system.⁴

Efficacy

Most research has been done on human cells or animals,⁵ but controlled studies in humans are being undertaken. Preclinical and/or early clinical studies indicate that Reishi has been shown to support:

• Healthy glucose metabolism^6,7
• Healthy liver function⁸
• Sleep³

Safety

In most studies, Reishi is well tolerated by participants. This was born out in research that analyzed the experience of volunteers, as well as their biochemistry.⁹

References

1. Ahmad, M.F. Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement. Biomed Pharmacother 107, 507-519 (2018).
2. Wachtel-Galor, S., Yuen, J., Buswell, J.A. & Benzie, I.F.F. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. in Herbal Medicine: Biomolecular and Clinical Aspects (eds. Benzie, I.F.F. & Wachtel-Galor, S.) (CRC Press/Taylor & Francis Copyright © 2011 by Taylor and Francis Group, LLC., Boca Raton (FL), 2011).
3. Cui, X.Y., et al. Extract of Ganoderma lucidum prolongs sleep time in rats. J Ethnopharmacol 139, 796-800 (2012).
4. Chu, Q.P., et al. Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism. Pharmacol Biochem Behav 86, 693-698 (2007).
5. Frost, M. Three Popular Medicinal Mushroom Supplements: A Review of Human Clinical Trials. BYU Faculty Publications 1609(2016).
6. Chu, T.T., et al. Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial. Br J Nutr 107, 1017-1027 (2012).
7. Gao, Y., Lan, J., Dai, X., Ye, J. & Zhou, S. A Phase I/II Study of Ling Zhi Mushroom Ganoderma lucidum (W.Curt.:Fr.)Lloyd (Aphyllophoromycetideae) Extract in Patients with Type II
   Diabetes Mellitus. International Journal of Medicinal Mushrooms – INT J MED MUSHROOMS 6, 33-40 (2004).
8. Gao, Y., et al. Protective Effect of Ganoderma (a Mushroom with Medicinal Properties) Against Various Liver Injuries. Food Reviews International 21, 27-52 (2005).
9. Wicks, S.M., et al. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. Am J Chin Med 35, 407-414 (2007).

Ziziphus (also known as Jujube, red date and Chinese date) has a long history of use in Traditional Chinese Medicine to calm the mind and reduce insomnia.¹ It is native to Asia and southern Europe. Ziziphus fruit has been used as a food and medicine for thousands of years in China,² where it is known as the “fruits of life.”³ Technically Ziziphus jujuba refers to the fruit of the plant and Ziziphus spinosa refers to the seeds found in the single hard kernel of the fruit. In Traditional Chinese Medicine, the seeds are most commonly used for sleep.¹

Constituents & Mechanisms of Action

Ziziphus seeds contains many bioactive compounds including:

• Alkaloids e.g. fragufoline, sanjoinin A
• Saponins e.g. jububosides
• Flavonoids e.g. spinosyn, epigallocatechin
• Alkaloids e.g. sanjoinine, zizyphusine
• Unsaturated fatty acids e.g. lauric acid, oleic acid, linoleic acid
• Amino acids e.g. proline, alanine, valine, glutamic acid

The bioactives in Ziziphus exert their effect partially via the GABA system in the brain. GABA is the main calming neurotransmitter and Ziziphus partially binds to the GABA-A receptors. The resultant chemical cascade in the brain promotes mild sleep induction while limiting receptor desensitization and thus the addictive effects often seen with pharmaceuticals such as Diazepam. Ziziphus also acts on the Serotonin system and may exert neuroprotection by inhibition of NMDA-induced cell death by inhibiting free radical generation³ it’s effect are likely to be greater than the sum of its parts.

Efficacy

Ziziphus improves sleeps, calming and protects neurons. When compared with Diazepam, Ziziphus is slower acting but lasts longer with less impairment of learning and memory and less addictive effects.¹ In fact, Ziziphus may improve memory.³ Ziziphus may also lower cholesterol and improve menopausal symptoms.³

Safety

While research is continuing, a low dose of Ziziphus may be effective and safe as an ongoing support for sleep,¹ with adverse effects similar to placebo.⁴

References

1. Shergis, J.L., et al. Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology. Phytomedicine : international journal of phytotherapy and phytopharmacology 34, 38-43 (2017).
2. Ji, X., et al. Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): A review. Food Chem 227, 349-357 (2017).
3. Rodríguez Villanueva, J. & Rodríguez Villanueva, L. Experimental and Clinical Pharmacology of Ziziphus jujuba Mills. Phytother Res 31, 347-365 (2017).
4. Yeung, W.F., et al. Chinese herbal medicine for insomnia: a systematic review of randomized controlled trials. Sleep Med Rev 16, 497-507 (2012).

Kava’s use as a ceremonial and medicinal¹ beverage in the South Pacific islands predates written history. J Pepping described this beautifully in his 1999 monograph published in the American Journal of Health-System Pharmacy: “Drinking a kava beverage has been described as inducing a “warm, pleasant and cheerful, but lazy feeling,” making people “sociable, though not hilarious or loquacious,” and not interfering with reasoning.”² Today Kava is used either socially by drinking a water-based extract or medicinally in capsule or tablet forms. When consumed socially, this is usually done in a semi-traditional manner as a water-extract served from a large communal bowl.³ Generally much higher doses are consumed when using Kava socially than when using Kava as a medicine. When used medicinally the dose of active constituents is usually standardized and have been extracted with alcohol, acetone or water.⁴ Kava is listed as an approved herb in the German Commission E monographs for the treatment of nervous anxiety, stress and restlessness.

Constituents & Mechanisms of Action

The bioactive compounds in Kava are known as kavalactones. At least 18 different kavalactones have been identified and are thought to be the main active compounds. However, Kava also contains other bioactive constituents, such as cinnamic acid, phenolics, flavones and fatty acids that may be important in its clinical effect.¹ Different preparation of Kava may contain different ratios of these compounds. The constituents in Kava are thought to act by enhancing the GABA system in the brain.

Efficacy

Kava extract may be effective in supporting:

• Calm mood in those suffering with anxiety⁶
• Female sexual performance and enjoyment⁷
• Sleep⁵
• Menopausal symptoms⁸

Safety

Long term Kava use has been associated with:

• Skin conditions such as dermatitis
• Depression
• Liver damage

However, studies and reports are inconsistent and may reflect the type of extraction, specific cultivar consumed, as well as traditional vs recreational use. It has been suggested that poor quality material could be responsible for liver toxicity.⁹ However, Kava can inhibit detoxification enzymes. So when Kava is taken with alcohol, medications or other substances, the result may be heightened toxicity of those substances.¹⁰

It is best not to use Kava in those with Parkinson’s disease or taking L-Dopa or drugs used to treat Parkinson’s. Kava, when used as a medicine, does not appear to have addictive effects.⁷

References

1. Showman, A.F., et al. Contemporary Pacific and Western perspectives on `awa (Piper methysticum) toxicology. Fitoterapia 100, 56-67 (2015).
2. Pepping, J. Kava: Piper methysticum. Am J Health Syst Pharm 56, 957-958, 960 (1999).
3. Baker, J.D. Pills, Potions, Products: Kava's Transformations in New and Nontraditional Contexts. The Contemporary Pacific 24, 233-265 (2012).
4. Côté, C.S., Kor, C., Cohen, J. & Auclair, K. Composition and biological activity of traditional and commercial kava extracts. Biochemical and Biophysical Research Communications 322, 147-152 (2004).
5. Sarris, J., Panossian, A., Schweitzer, I., Stough, C. & Scholey, A. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence.
   Eur Neuropsychopharmacol 21, 841-860 (2011).
6. Sarris, J., et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 33, 643-648 (2013).
7. Sarris, J., et al. Kava for the Treatment of Generalized Anxiety Disorder RCT: Analysis of Adverse Reactions, Liver Function, Addiction, and Sexual Effects. Phytotherapy Research 27, 1723-1728 (2013).
8. Huntley, A.L. & Ernst, E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause 10, 465-476 (2003).
9. Teschke, R. & Lebot, V. Proposal for a Kava Quality Standardization Code. Food and Chemical Toxicology 49, 2503-2516 (2011).
10. Toohey, T.P., Lu, B.Y. & Wada, C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava: report of 2 cases. Prim Care Companion CNS Disord 15(2013).

Magnolia bark has been used for thousands of years in Traditional Chinese and Japanese medicines to treat a variety of disorders including anxiety, insomnia, depression and stomach upsets.¹

Constituents & Mechanisms of Action

Over 250 compounds have been isolated from the Magnolia plant including a variety of terpenes, flavonoids, alkaloids and lignans. The main bioactive compound appears to be the lignans, magnolol and honokiol.¹ The constituents of Magnolia bark have anti-inflammatory, anti-microbial, anti-oxidant actions, as well as being supporting brain health, heart health and metabolic health.² Magnolia appears to have a GABA like effect in the brain³, promoting calmness. It also actives the receptors of the human endocannabinoid system. Although this does need to be further investigated.⁴

Efficacy

Most controlled studies have been done in test tubes or in animals. Early research suggests that Magnolia may improve:

• Anxiety⁵
• Sleep⁶
• Cognition⁷
• Metabolism⁸

Safety

Magnolia has been found to be safe in animal studies, even at high doses.⁹

References

1. Poivre, M. & Duez, P. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents. J Zhejiang Univ Sci B 18, 194-214 (2017).
2. Zhang, J., et al. Insights on the Multifunctional Activities of Magnolol. Biomed Res Int 2019, 1847130 (2019).
3. Han, H., et al. Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx. Journal of medicinal food 14, 724-731 (2011).
4. Rempel, V., et al. Magnolia Extract, Magnolol, and Metabolites: Activation of Cannabinoid CB2 Receptors and Blockade of the Related GPR55. ACS Med Chem Lett 4, 41-45 (2013).
5. KURIBARA, H., KISHI, E., HATTORI, N., OKADA, M. & MARUYAMA, Y. The Anxiolytic Effect of Two Oriental Herbal Drugs in Japan Attributed to Honokiol from Magnolia Bark. Journal of Pharmacy and Pharmacology 52, 1425-1429 (2000).
6. Chen, C.R., et al. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice. Neuropharmacology 63, 1191-1199 (2012).
7. Lee, Y.K., et al. Protective effect of the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity. J Nat Med 63, 274-282 (2009).
8. Zhang, Z., et al. The magnolia bioactive constituent 4-O-methylhonokiol protects against high-fat diet-induced obesity and systemic insulin resistance in mice. Oxidative medicine and cellular longevity 2014, 965954 (2014).
9. Liu, Z., et al. Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats. Regul Toxicol Pharmacol 49, 160-171 (2007).

Gamma-aminobutyric acid (GABA) is a naturally occurring compound made in our bodies and found in foods such as tea and mushrooms. GABA can also be taken as a supplement.

GABA in the Body

Gamma-aminobutyric acid (GABA) is a naturally occurring amino acid that is made in the body. GABA is mostly known as the main inhibitory neurotransmitter in the brain while glutamate is the main excitatory neurotransmitter. Neurotransmitters are compounds that are found in neurons (brain cells). They act as chemical messengers, relying information from one neuron to the next resulting in an action. Neurotransmitters will either “fire up” a target cell (another neuron, muscle cell or hormone producing cell) or will dampen it down. The balance of the firing up (excitation) and the dampening down (inhibition) is of paramount importance in general and mental health. Too much firing up (excitation) can lead to agitation, distraction and to significant psychiatric disorders, while too much dampening down (inhibition) can lead to low mood and lethargy. Conversely too little inhibition leads to anxiety and insomnia.¹ Furthermore, neurotransmitters affect each other. Scientists are still investigating the complex neurotransmitter system and how this affects behavior.² GABA, the main inhibitory neurotransmitter is thought to support the “ability to stay focused on selected features of objects with suppression of behavioral reactivity to other features” as well as the “speed of integration of an action in physical manipulations with objects with well-defined scripts of actions.”² GABA is made in the neuron from glutamate with the help of Vitamin B6.³ It then sits in little vesicles (membrane sacs) waiting for a signal. Once the signal is received, GABA is released from the cell into the space between two cells (synapse). It then attaches to a receptor on the receiving cell where it inhibits firing. Although the brain is much more complex that a simple balance between neurotransmitters, in general the balance between excitation (glutamate) and inhibition (GABA) swings towards excitation, we may suffer anxiety,⁴ have difficulty sleeping and even difficulty concentrating.¹ Activating GABA receptors has long been used in pharmacology and plant medicine to help with sleep.^1,5 GABA is not only made in the brain but is also made in the gut but “good” gut bacteria in the gut microbiome.⁶ GABA seems send message from the gut to the brain via the vagus nerve.⁷

GABA in Food & Drink

GABA is found in tea, especially in white tea, cruciferous vegetables, spinach, tomato, mushroom and sprouted beans and grains.⁸

GABA as a Supplement

Taking GABA has been shown to have a positive effect on sleep.⁹ It also helps to decrease the stress that is induced by mental tasks,¹⁰ as well as supporting the nervous system, inducing relaxation. Supplementing GABA may “help to distribute limited attentional resources more efficiently.”¹¹

References

1. Savage, K., Firth, J., Stough, C. & Sarris, J. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32, 3-18 (2018).
2. Trofimova, I. & Robbins, T.W. Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry. Neuroscience and biobehavioral reviews 64, 382-402 (2016).
3. Jewett BE, S.S. Physiology, GABA, (Treasure Island (FL): StatPearls Publishing, 2020).
4. Wong, C.G., Bottiglieri, T. & Snead, O.C., 3rd. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol 54 Suppl 6, S3-12 (2003).
5. Gottesmann, C. GABA mechanisms and sleep. Neuroscience 111, 231-239 (2002).
6. Yunes, R.A., et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42, 197-204 (2016).
7. Bravo, J.A., et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108, 16050-16055 (2011).
8. Briguglio, M., et al. Dietary Neurotransmitters: A Narrative Review on Current Knowledge. Nutrients 10(2018).
9. Yamatsu, A., et al. The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract. J Nutr Sci Vitaminol (Tokyo) 61, 182-187 (2015).
10. Yoto, A., et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331-1337 (2012).

Magnesium is necessary for every major biological process and is especially important in the activation of vitamins which go on to perform many important functions that support your cells and your life. Magnesium is found in beans, nuts, grains and green leafy vegetables as well as red meat and fish, with small amounts in water. However, Magnesium absorption is generally from plant food sources due to the phytates and oxalates found in plant foods especially when insufficiently prepared. The stressors of modern life and lower levels of magnesium in our food¹ due to poor soils and processing, make us especially vulnerable to magnesium insufficiency. We need to consume magnesium regularly to keep magnesium sufficient.² Magnesium plays a key role in the regulation of sleep, improving all aspects of sleep. This is thought to be by both enhancing GABA (calming brain chemical) and inhibiting NMDA. Magnesium citrate is also described as mildly sedating.

Magnesium Actions

Magnesium is involved in more than 300 essential reactions including:

• Activation of enzymes without which there would be no life.² These enzymes go on to perform functions such as:
  •  Making ATP, the energy molecules that allow the body to function (Mitochondrial ATP synthase).
  • Creating a beneficial charge across cell walls. Amongst other actions, this allows the transport of compounds such as glucose and other nutrients into the cell and supports nerve cells to fire correctly (Na + /K + -ATPase)
  • Utilizing food for energy (Hexokinase, Phosphofructokinase, Tyrosine Kinase on the insulin receptor)
  • Generating phosphocreatine for energy use and recycling of ATP (Creatine kinase)
  • Translating signals outside the cell into responsive actions inside the cells (Adenylate cyclase)
• Energy production
  • The breakdown and utilization of carbohydrates, protein, and fats to make ATP both in the aerobic pathway (oxidative phosphorylation) and anaerobic pathway (glycolysis)
  • ATP mainly exists as a complex with magnesium
• Synthesis of glutathione, the most important anti-oxidant in cells
• Antagonises calcium to support:
  • Blood vessel tone
  • Muscular contraction and relaxation
  • Release of neurotransmitters and “firing” of neurons (brain cells)
• Heart health
  • Protects heart cells from stress
  • Regulates potassium in heart cells
  • Reduces clumping of blood cells
• Cell health
  • Regulates cell movements
• Structural: Magnesium is an important structural element of:
  • Bones
  • Protein tissue such as muscle
  • DNA
  • Mitochondria (energy factories of the cells)
• Activation of other nutrients:
  • Vitamin D (Vitamin D also increases Magnesium absorption)
  • B-vitamins

Magnesium in the Body

Magnesium is the fourth most abundant mineral in the body,³ with 50% found in bone. 49% is found inside tissues and organs where it is bound to protein and to ATP, with only 1% being found in blood. Magnesium is lost from the body through mainly through urine but also through feces and sweat. The kidneys play a critical role in controlling the amount of magnesium in the body by controlling how much magnesium is lost in the urine. An average 70kg adult will have around 24 grams of magnesium in their body.  Research shows that nearly two-thirds of the people in the Western World, do not achieve the recommended daily allowance for magnesium.⁴ Stress, whether physical or emotional increases the need for magnesium.⁵ Furthermore, many medications cause loss of magnesium in the urine,² leaving many with a triple whammy. Ongoing magnesium deficiency is associated with many chronic and metabolic diseases including high blood pressure, heart disease, stroke, imbalanced cholesterol, insulin resistance, osteoporosis, depression, and insomnia. Furthermore, magnesium deficiency may help link inflammation, oxidative stress and aging. Sufficient magnesium is critical to overall health and neurological health, supporting sleep.

Magnesium in the World

Magnesium is the 8th most common element in the earth’s crust where it is most often found as magnesium carbonate or dolomite. However, most biologically available magnesium in the sea and the rivers. Due to the electromagnetic activity of magnesium, it naturally occurs in combination with other compounds

Magnesium Citrate

This form of magnesium has been chosen by Omic as it better absorbed and is more soluble than some other types of magnesium.⁶

References

1. Guo, W., Nazim, H., Liang, Z. & Yang, D. Magnesium deficiency in plants: An urgent problem. The Crop Journal 4, 83-91 (2016).
2. Gröber, U., Schmidt, J. & Kisters, K. Magnesium in Prevention and Therapy. Nutrients 7, 8199-8226 (2015).
3. Boomsma, D. The magic of magnesium. International journal of pharmaceutical compounding 12, 306-309 (2008).
4. Schwalfenberg, G.K. & Genuis, S.J. The Importance of Magnesium in Clinical Healthcare. Scientifica (Cairo) 2017, 4179326 (2017).
5.  Seelig, M.S. Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review). Journal of the American College of Nutrition 13, 429-446 (1994).
6. Walker, A.F., Marakis, G., Christie, S. & Byng, M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res 16, 183-191 (2003).