MONOGRAPH PRO Destress - AOR

MO NO GR A P H

Non-Drowsy Cal m ing Fo rm ul a

PRO Destress

aor.c a

D80194_AOR_Marketing_ProMonograph_Destress.indd 1 2019-08-29 9:42 AM

MONOGR AP H PRO DESTRESS

aor.ca p.2

ABOUT AORAdvanced Orthomolecular Research (AOR) is a Canadian company headquartered in Calgary, Alberta. AOR has anestablished reputation as the most advanced supplement formulator in the country and around the world. It is through ethical discipline and evidenced-based science that we lead and advance the natural health industry. For more information, please visit aor.ca.

ABOUT AOR’ S PRO S E RIE SThe Professional Series provides unique formulations to meet the needs of health care professionals. The Professional Series is exclusive to clinicians, it is not available in any retailer stores or online. Formulations are designed to address specific clinical concerns with the appropriate forms of ingredients, sources, and dosages for therapeutic benefits in a number of diseases and preventative processes. Created by practicing NDs that are guided by the latest research and clinical experience, the Professional Series still includes time tested favourites as well as unique and innovative formulations.

AOR PROD UCT PAT HFrom raw material selection to manufacturing and shipping of final packaged goods, AOR adheres to the strictest of quality control standards. AOR products represent innovative ideas and thoughtfully researched concepts with advanced techniques to develop products of superior quality and effectiveness, bringing you “innovation you can trust”.

Use only the minimal required non-medicinal ingredients (NMI) when

necessary. Where possible we use NMI declared

“clean-label”

Packaging and Labeling



aor.ca p.3

SUPPLEM E N T FACTS

NPN: 80068905

AOR34402 90 capsules

Serving Size: 1 capsule

Medicinal Ingredients:GABA (gamma-aminobutyric acid) 100 mg L-Theanine 250 mg Holy Basil extract (10:1) 200 mg

Non-medicinal Ingredients: microcrystalline cellulose, sodium stearyl fumarate, hyprolose, silicon dioxide, maltodextrin. Capsule: hypromellose.

Suggested Dose: Take one capsule daily with/without food, or as directed by a qualified health care practitioner.

Cautions: Do not use if you are pregnant. Consult a health care practitioner prior to use if you are breastfeeding, taking heart or blood pressure medication, if you have a heart condition, diabetes, or if symptoms persist or worsen.

Sources: Ocimum sanctuim (Holy basil) botanical extract Camillia sinensis botanical extract Pharmaceutical synthesis

DestressPromotes Calm & Relieves Worry

P RODUCT S P OTLIGHT


p.4


aor.ca

SUMMARYPro Destress is a fast-acting and long-lasting anxiolytic for anxiety, stress, and onset insomnia, particularly in those that dealing with phase II adrenal dysfunction. It works to calm excess sympathetic tone with GABA, L-theanine, and the adaptogen Holy Basil. Holy Basil has been reported to induce relaxation, promote a feeling of calm, and reduce stress, both as an acute treatment while also addressing the underlying dysfunction. While sources of L-theanine have been used for centuries, it is only recently that it has been identified as the amino acid associated with increased alpha waves resulting in an alert, yet calming effect. Finally, GABA is a well-understood inhibitory neurotransmitter, prescribed in the treatment of a variety of nervous system disorders, most notably insomnia and anxiety.

BACKGROUNDThe stress response is an essential adaptive survival mechanism, designed to rapidly provide the necessary energy, strength, and stamina to fight or flight. In present-day society, this short-term response can become chronic, due to perceived physical or psychological threats to acceptance and stability. It has been estimated that over 75% of all disease is consequence to chronic stress with more than 66% of all visits to primary-care physicians related to stress induced disorders.1 Depression, anxiety disorders, cardiovascular disease, metabolic syndrome, chronic digestive complaints, decreased immunity and even cancer have all been attributed to the downstream effects of chronic stress.1,2

Upon initiation of stress, the autonomic nervous system downregulates the parasympathetic tone in order to redirect resources and increase sympathetic stimulation, recruiting a variety of autonomic responses. The activation of the hypothalamic-pituitary-adrenal (HPA) axis results in a neuroendocrine cascade, which increases catecholamines (dopamine, norepinephrine, epinephrine), glucocorticoids (cortisol) and mineralocorticoids (aldosterone) to meet physiological, psychological and behavioural demand. With long-term activation, the HPA axis can become dysfunctional, leading to alterations in cortisol rhythms and poor adrenal output, commonly known as “adrenal fatigue”. Furthermore, dysregulation of excitatory and inhibitory neurobiological pathways occurs as GABA, endogenous opioids, and serotonin become depleted.1,3 These neurochemical changes are responsible for common symptoms associated with chronic stress, including fatigue, anxiety, irritability, sleeping disorders, emotional instability and concentration problems.4

Treatment strategies to address the underlying pathophysiology of chronic stress target the HPA axis, neurotransmitter balance and downstream metabolic effects. Gamma-aminobutyric acid (GABA) is an amino acid that acts as an inhibitory neurotransmitter with the capacity to exhibit anxiolytic effects. Impairments in GABA-mediated inhibition are seen in various neurological and psychological conditions, such as insomnia and anxiety disorders.3 GABA receptors are found in every region of the human brain and is peripherally distributed in the enteric nervous system (ENS).3 Recent studies reveal oral supplementation of GABA indirectly exerts anxiolytic effects on the CNS by modulating the vagus nerve and gut microbiota. L-theanine, an amino acid typically found in green tea, has a number of neuroregulatory effects, able to combat both acute and long-term stress. L-theanine has been shown to reduce symptoms of anxiety, improving the ratio between alpha and beta brain waves and block glutamate receptors to dampen excitatory signalling.5

The use of adaptogens provides significant relief from both acute and chronic effects of chronic HPA dysregulation seen with stress. Holy Basil, a common Ayurvedic herb that belongs to the Lamiaceae family, possesses a range of actions, including adaptogenic, antioxidant and anti-inflammatory properties. Notably, Holy Basil can act as a neuroprotectant, able to reduce free radicals and stress associated glucose spikes to protect macromolecules from oxidative damage and dysglycemia.4


p.5


aor.ca

CLINICAL ST UD IE SSTRESS AND ANXIETY

During an eight-week, double-blind randomized, placebo-controlled (RCT) trial, 40 patients with DSM-IV schizophrenia or schizoaffective disorder were given L-theanine (400 mg/d) in addition to their antipsychotic regiment. Those treated with L-theanine had a significant reduction in anxiety scores.6 A similar study showed improved serum levels of brain-derived neurotrophic factor (BDNF) and cortisol-to-DHEAS ratio, which the author attributed to the anxiolytic effects of L-theanine.7 In addition, these studies show the safety profile of L-theanine in combination with antipsychotic medication.

In a double-blind, placebo-controlled, balanced crossover study, the effects of 200 mg L-theanine on stress were measured using magnetoencephalography (MEG). Participants (n=34) were put under stressful scenarios and evaluated for markers of stress, including brain waves, salivary cortisol and the State-Trait Anxiety Inventory questionnaire. Two hours after administration those categorized as “high anxiety” showed a significant increase in alpha brain waves compared to the placebo group.8 Alpha waves are characterized by a relaxed wakefulness, while beta waves are typical in highly stressful situations. Additional studies show improvements in secretory immunoglobulin A (IgA) levels, heart rate variability and blood pressure with the administration of L-theanine, indicating its ability to reduce the sympathetic response to acute stress.10,11

GABA is shown to have similar anxiolytic effects as L-theanine. In a randomized, single blind, placebo-controlled, crossover study (n=63), those who received 100 mg of GABA showed a significant increase in alpha waves and decrease in beta waves, 60 minutes post-administration.12 These effects were reproducible in other studies, showing that GABA can effectively improve parameters of stress, including; heart rate variability scores and salivary chromogranin A (CgA), psychological fatigue and IgA during stressful stimuli.1,13,14

Holy Basil has been reported to promote relaxation, improve anxiety and symptoms of stress. Thirty-five participants were given a 500 mg capsule of standardized Holy Basil, twice daily for 60 days. According to the modified Hamilton’s brief psychiatric rating scale, Holy Basil significantly improved symptoms of stress (27.5%), depression (30.5%) and generalized anxiety (34.2%).15 In a randomized, double-blind, placebo-controlled study, participants (n = 71) were given 1200 mg of a Holy Basil extract for six weeks. After six weeks of intervention, Holy Basil was 39% more effective in reducing symptoms of stress compared to placebo. Overall, improvements in forgetfulness, sexual problems of recent origin, exhaustion and sleep problems significantly improved (P ≤ 0.05).4 In an animal study, Holy Basil was shown to reduce serum concentrations of cortisol and glucose; prevent lipid peroxidation associated with dysglycemia, and prevent stress induced reductions in hippocampal acetylcholine, which are attributed to short-term memory loss during chronic stress.16,17

SLEEP DISTURBANCES

In an open-label clinical study in patients with major depressive disorder (MDD), those given (n=20) 250 mg of L-theanine for eight weeks showed a significant decrease in sleep disturbances according to the Pittsburgh Sleep Quality Index (PSQI). In addition, no interactions were found with concurrent antidepressant therapy.18

A randomized, double-blind, placebo-controlled trial was conducted involving boys diagnosed with ADHD. Participants (n=46) were given 400 mg of L-theanine in divided doses for six weeks. Based on changes reported from The Pediatric Sleep Questionnaire (PSQ), those who consumed L-theanine obtained significantly higher sleep percentage, defined as time spent in restful sleep, compared to the placebo group.19



aor.ca p.6

PH ARMAC O LO GYMECHANISMS OF ACTION

Gamma-aminobutyric acid (GABA) is an amino acid that acts in the central nervous system (CNS) as an inhibitory neurotransmitter, binding GABA receptors to exert anxiolytic effects.3 Substantial controversy surrounds GABA’s ability to cross the blood brain barrier (BBB) and its exact mechanism of action. Although recent evidence has identified and confirmed the presence of a GABA transporter in the BBB, the delivery of orally administered GABA has yet to be identified.20 Based on the latest discoveries between the gut-brain axis, additional hypotheses have developed to explain the anxiolytic effects of orally administered GABA confirmed by MEG analysis. GABA receptors are expressed in a variety of peripheral tissues, including the digestive tract. Particular strains of bacteria present in the microbiome, such as Lactobacillus rhamnosus, are shown to produce GABA. Furthermore, transcutaneous vagus nerve stimulation is shown to increase GABA production. Based on these mechanisms it is possible that oral GABA may interact with the microbiome to influence cortical GABA levels through afferent vagal stimulation.21

L-theanine is an amino acid with neuroregulatory effects. Due to its similar structure to glutamate, theanine is able to modulate NMDA receptors to prevent overstimulation of the excitatory glutamate pathway. In addition, theanine increases GABA, dopamine, and glycine and reduces serotonin, lending a focused, yet calm effect.8,19

Numerous active constituents of Holy Basil have been identified, including; eugenol, ursolic acid, rosmarinic acid and luteolin. Of these, eugenol has received considerable attention for its ability to reduce serum glucose, triglycerides and cholesterol levels.22 Furthermore, extracts of Holy Basil are shown to increase the production of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), to inhibits neuronal death, lipid peroxidation and DNA damage associated with stress induced oxidative stress.23



aor.ca p.7

PH ARMAC O K INE T ICS, ADVERSE EFFECTS, AND INTER ACTIONSPHARMACOKINETICS

Oral dosing of GABA shows rapid absorption and peak plasma concentrations approximately one to one and a half hours after administration. The elimination half-life is five to 5.2 hours.21

L-theanine is actively transported across the BBB within 20-30 minutes after administration, reaching peak concentrations between 30 and 120 minutes. Levels decrease after approximately five hours after administration as the amino acid is metabolized by the kidneys into glutamate and ethylmaine.5,8,10

ADVERSE EFFECTS

Long-term administration of GABA (120 mg) shows no adverse effects. Studies using high dosages of GABA (18 g for four days) report sore throat, skin burning sensation, headache and dizziness.1,12 L-theanine is generally considered well tolerated and safe, with no adverse effects reported. Holy Basil administration at 1200 mg for six weeks was found to be well tolerated in stress patients with no adverse events reported.24

Holy Basil is known to have antispermatogenic or antifertility effects and has been used traditionally to stimulate uterine contractions. Therefore, Holy Basil should be avoided in patients trying to conceive or those who are pregnant or breastfeeding.25-28

INTERACTIONS

In studies that combined GABA or L-theanine with antipsychotics, antidepressants or Ritalin, no adverse interactions were reported.29,30 Animal studies have shown that Holy Basil may cause hypoglycemia and prolonged bleeding time; therefore, Pro Destress should be used with caution or avoided in patients with hypoglycemia, bleeding disorders or those taking anticoagulants.31,32 In addition, those with a known hypersensitivity to the Lamiaceae family should avoid use.

DOSAGEPro Destress contains 100 mg GABA, 250 mg L-theanine and 200 mg of a standardized 10:1 extract of Holy Basil. For general therapy, the suggested dose range is one to two caps twice per day for chronic stress, adrenal dysfunction and insomnia. For acute anxiety one to two caps may be used as needed, up to six capsules per day. This is based on the therapeutic range of the ingredients and max dose of L-theanine.5



aor.ca p.8

CLINICAL APPL ICAT ION S• Anxiety• Insomnia – onset, maintenance• Improve resilience to stress and recovery from chronic stress • Prevent memory deficits associated with high cortisol• Glutamate excess and protection from neurotoxins• Oxidative stress in chronic disease (cardiovascular disease, diabetes, TBI)• Cholesterol imbalances and lipid peroxidation• Anti-diabetic and glycemic lowering effects • Hypertension related to chronic stress

CONCLUSIO NFrom the literature and effects of the ingredients reviewed, Pro Destress is safe and effective in the management of both acute and chronic stress-induced physiological changes. Anxiolytic effects typically take place within 20 to 30 minutes, with long-term physiological changes in brain waves, cortisol and glucose seen up to three hours post consumption. With prolonged use beyond six weeks, improvements may be seen in metabolic parameters, serum cholesterol and lipid profiles, for the treatment of diabetes and glycemic control. It offers both neuro- and hepatoprotective effects. This fast-acting formula is safe, natural and non-drowsy for an effective option in the management of the effects of chronic stress.

For a complete stress-reduction protocol, use in combination with: PRO Adapt, PRO B complex, and Magnesium Synergy.


p.9


aor.ca

REFEREN CE S1. Abdou, A.M., Higashiguchi, S., Horie, K., Kim, M., Hatta, H., and Yokogoshi, H. Relaxation and immunity enhancement effects of

y-Aminobutyric acid (GABA) administration in humans. BioFactors 26, 201–208.

2. Chatterjee, M., Verma, P., Maurya, R., and Palit, G. (2011). Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression. Pharm. Biol. 49, 477–483.

3. Savage, K., Firth, J., Stough, C., and Sarris, J. (2018). GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother. Res. 32, 3–18.

4. Saxena, R.C., Singh, R., Kumar, P., Negi, M.P.S., Saxena, V.S., Geetharani, P., Allan, J.J., and Venkateshwarlu, K. (2012). Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study. Evid.-Based Complement. Altern. Med. ECAM 2012.

5. Adhikary, R., and Mandal, V. (2017). l-theanine: A potential multifaceted natural bioactive amide as health supplement. Asian Pac. J. Trop. Biomed. 7, 842–848.

6. Ritsner, M.S., Miodownik, C., Ratner, Y., Shleifer, T., Mar, M., Pintov, L., and Lerner, V. (2011). L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J. Clin. Psychiatry 72, 34–42.

7. Miodownik, C., Maayan, R., Ratner, Y., Lerner, V., Pintov, L., Mar, M., Weizman, A., and Ritsner, M.S. (2011). Serum Levels of Brain-derived Neurotrophic Factor and Cortisol to Sulfate of Dehydroepiandrosterone Molar Ratio Associated With Clinical Response to l-theanine as Augmentation of Antipsychotic Therapy in Schizophrenia and Schizoaffective Disorder Patients. Clin. Neuropharmacol. 34, 155–160.

8. White, D.J., de Klerk, S., Woods, W., Gondalia, S., Noonan, C., and Scholey, A.B. (2016). Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients 8.

9. Lu, K., Gray, M.A., Oliver, C., Liley, D.T., Harrison, B.J., Bartholomeusz, C.F., Phan, K.L., and Nathan, P.J. (2004). The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum. Psychopharmacol. 19, 457–465.

10. Kimura, K., Ozeki, M., Juneja, L.R., and Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biol. Psychol. 74, 39–45.

11. Yoto, A., Motoki, M., Murao, S., and Yokogoshi, H. (2012). Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J. Physiol. Anthropol. 31, 28.

12. Yoto, A., Murao, S., Motoki, M., Yokoyama, Y., Horie, N., Takeshima, K., Masuda, K., Kim, M., and Yokogoshi, H. (2012b). Oral intake of y-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331–1337

13. Nakamura, H., Takishima, T., Kometani, T., and Yokogoshi, H. (2009). Psychological stress-reducing effect of chocolate enriched with y-aminobutyric acid (GABA) in humans: assessment of stress using heart rate variability and salivary chromogranin A. Int. J. Food Sci. Nutr. 60, 106–113.

14. Kanehira, T., Nakamura, Y., Nakamura, K., Horie, K., Horie, N., Furugori, K., Sauchi, Y., and Yokogoshi, H. (2011). Relieving occupational fatigue by consumption of a beverage containing y-amino butyric acid. J. Nutr. Sci. Vitaminol. (Tokyo) 57, 9–15.

15. Bhattacharyya, D., Sur, T.K., Jana, U., and Debnath, P.K. (2008). Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Med. Coll. J. NMCJ 10, 176–179.

16. Gholap, S., and Kar, A. (2004). Hypoglycaemic effects of some plant extracts are possibly mediated through inhibition in corticosteroid concentration. Pharm. 59, 876–878.


p.10


aor.ca

REFEREN CE S (continued)

17. Sembulingam, K., Sembulingam, P., and Namasivayam, A. (2005). Effect of Ocimum sanctum Linn on the changes in central cholinergic system induced by acute noise stress. J. Ethnopharmacol. 96, 477–482.

18. Hidese, S., Ota, M., Wakabayashi, C., Noda, T., Ozawa, H., Okubo, T., and Kunugi, H. (2017). Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr. 29, 72–79.

19. Lyon, M.R., Kapoor, M.P., and Juneja, L.R. (2011). The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern. Med. Rev. J. Clin. Ther. 16, 348–354.

20. Kakee, A., Takanaga, H., Terasaki, T., Naito, M., Tsuruo, T., and Sugiyama, Y. Efflux of a suppressive neurotransmitter, GABA, across the blood–brain barrier. J. Neurochem. 79, 110–118.

21. Li, J., Zhang, et al. (2015). Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics. Front. Pharmacol. 6.

22. Prakash, P., and Gupta, N. (2005). Therapeutic uses of Ocimum sanctum Linn (Tulsi) with a note on eugenol and its pharmacological actions: a short review. Indian J. Physiol. Pharmacol. 49, 125–131.

23. Venuprasad, M.P., Kumar, K.H., and Khanum, F. (2013). Neuroprotective Effects of Hydroalcoholic Extract of Ocimum sanctum Against H202 Induced Neuronal Cell Damage in SH-SY5Y Cells via Its Antioxidative Defence Mechanism. Neurochem. Res. 38, 2190–2200.

24. Yates, B. Holy Basil – An Overview of the Research and Clinical Indications. 10.

25. Jamwal, S., Singh, S., Gill, J.S., and Kumar, P. (2017). L-theanine prevent quinolinic acid induced motor deficit and striatal neurotoxicity: Reduction in oxido-nitrosative stress and restoration of striatal neurotransmitters level. Eur. J. Pharmacol. 811, 171–179.

26. Baliga, M.S., Jimmy, R., Thilakchand, K.R., Sunitha, V., Bhat, N.R., Saldanha, E., Rao, S., Rao, P., Arora, R., and Palatty, P.L. (2013). Ocimum sanctum L (Holy Basil or Tulsi) and its phytochemicals in the prevention and treatment of cancer. Nutr. Cancer 65 Suppl 1, 26–35.

27. Jayanti, I., Jalaluddin, M., Avijeeta, A., Ramanna, P.K., Rai, P.M., and Nair, R.A. (2018). In vitro Antimicrobial Activity of Ocimum sanctum (Tulsi) Extract on Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. J Contemp Dent Pract 19, 415–419.

28. Sen, P., Maiti, P.C., Puri, S., Ray, A., Audulov, N.A., and Valdman, A.V. (1992). Mechanism of anti-stress activity of Ocimum sanctum Linn, eugenol and Tinospora malabarica in experimental animals. Indian J. Exp. Biol. 30, 592–596.

29. Boonstra, E., de Kleijn, R., Colzato, L.S., Alkemade, A., Forstmann, B.U., and Nieuwenhuis, S. (2015). Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front. Psychol. 6.

30. Kurihara Set al. Cystine and theanine: amino acids as oral immunomodulative nutrients. Springerplus. 2013 Nov 26;2:635.

31. Rao, L. (2012). Efficacy of Ocimum sanctum for Relieving Stress: A Preclinical Study. The Journal of Contemporary Dental Practice 782–786.

32. Sakina, M.R., Dandiya, P.C., Hamdard, M.E., and Hameed, A. (1990). Preliminary psychopharmacological evaluation of Ocimum sanctum leaf extract. J Ethnopharmacol 28, 143–150.



aor.ca p.1 1

Notes


MONOGRAPH PRO Destress - AOR

Documents

Transcript of MONOGRAPH PRO Destress - AOR