PRODUCT FACTS – CALM DOGS® FORMULA

THE SCIENCE BEHIND CALM DOGS®

Calm Dogs Veterinary Formula Maximum Strength Calming Aid for Dogs
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PRODUCT FACTS – CALM DOGS® FORMULA

Ashwagandha is perhaps best known for its ability to reduce stress. Researchers have reported that it blocks the stress pathways by regulating chemical signaling in the nervous system. Research has shown that Ashwagandha can play an important role in treating neurological disorders associated with GABAergic signaling dysfunction such as general anxiety disorders. (1), (22), (23)

Chamomile is widely regarded as a mild tranquilizer due to a flavonoid, apigenin, that binds to benzodiazepine receptors in the brain. Chamomile has been reported to treat generalized anxiety disorder (GAD). Chamomile showed significant inhibition of GAD activity in clinical studies. Recent results from controlled clinical trials on Chamomile extract for GAD show that it has anxiolytic activity GAD. (2), (3), (22)

Ginger Root is shown to relieve nausea and vomiting. According to a review of twelve studies, ginger can significantly reduce symptoms of nausea. This can greatly affect dogs with stomach upset in stressful situations like travel and car rides. (4), (24), (25)

Kava’s ability to create physical and mental calmness is attributed to all six of the main lactones found in Kava. kavalactones have been shown to bind to the receptors in the part of the brain responsible for relaxation. Research has shown Kava has the ability to reduce feelings of anxiety and promote a sense of calm. Studies show that kavain and the other kavalactones interact with the limbic system, the part of our brains most associated with emotions, emotional behavior, and motivation. The amygdala is the part of the limbic system that regulates feelings of fear and anxiety. Kavalactones are shown to bind to receptors in that part of the brain, making Kava one of nature’s best natural relaxants. The pharmacological properties of Kava are postulated to include blockade of voltage-gated sodium ion channels, enhanced ligand binding to gamma-aminobutyric acid (GABA) type A receptors, diminished excitatory neurotransmitter release due to calcium ion channel blockade, reduced neuronal reuptake of noradrenaline (norepinephrine), reversible inhibition of monoamine oxidase B and suppression of the synthesis of the eicosanoid thromboxane A(2), which antagonizes GABA(A) receptor function. Multiple clinical studies have shown that Kava and kavalactones are effective in treating anxiety. (5), (22)

Lemon Balm, even a single dose, increases calmness and alertness in situations of mental stress. Multiple other studies have shown that Lemon Balm reduces anxiety and improves memory and alertness during periods of mental stress. Research attention has turned to the bioactive properties of Lemon Balm, including its effects on the central nervous system and its neurocognitive effects, cholinergic nicotinic and muscarinic receptor binding in the brain. Additional studies showed Lemon Balm has a sedative/anxiolytic effect similar to medications like Valium and Xanax but without the unwanted side effects of prescription benzodiazepines. The mood/anxiolytic effects of lemon balm are thought to be attributable to known interactions with GABA-A receptors. (6), (22)

Melatonin has neuroprotective effects and has been tested in many animal models, including models of Parkinson’s disease, Alzheimer’s disease, stroke, and chemical toxicities. The outcome of these studies provides evidence that Melatonin proves very important in reducing the loss of neurons and glia under pathophysiological conditions. The results of clinical trials performed within the last half-decade support this conclusion. Some of the major actions of Melatonin are mediated at the mitochondrial level, such as the action of free radical avoidance. Melatonin is often used to produce relaxation and help with insomnia. Overall, Melatonin has been used in dogs to decrease anxiety and stress. It is also used to reduce pre and post-operative anxiety and stress. (7), (26)

Omega-3 is necessary for many substances to pass the blood-brain barrier. Omega-3 fatty acid supplements help ease anxiety symptoms in people diagnosed with a range of physical and mental health problems, according to a review published in the Sept. 14, 2018, JAMA Network Open. The report pooled findings from nineteen different studies and included 1,200 people. Most of the studies compared Omega-3 supplements to a placebo. Researchers found that people who took Omega-3 reduced anxiety symptoms. Omega-3 fatty acids, which are derived from fish oil, have several biological effects on the body. Brain membranes contain a high proportion of these fats. Human studies suggest that a lack of Omega-3s in the brain may induce various behavioral and psychiatric disorders. (8), (27)

Passionflower (Passiflora incarnata) was used traditionally in the Americas and later in Europe as a calming herb for anxiety, insomnia, seizures, and hysteria. It is still used today to treat anxiety and insomnia. Scientists believe passionflower works by increasing levels of a chemical called gamma-aminobutyric acid (GABA) in the brain. GABA lowers the activity of some brain cells, making you feel more relaxed.

Studies of people with generalized anxiety disorder show that Passionflower is as effective as the drug oxazepam (Serax) for treating symptoms. Passionflower, however, produced less impairment on job performance than oxazepam. Other studies show that those who were given Passionflower before surgery had less anxiety than those given a placebo. (9), (22)

Valerian Root is referred to as “nature’s Valium.” This herb has been used since ancient times to promote tranquility and improve sleep. Valerian Root has received attention for its interaction with gamma-aminobutyric acid (GABA.) This chemical messenger helps regulate nerve impulses in your brain and nervous system. Researchers have shown that low GABA levels related to acute and chronic stress are linked to anxiety. Valerian Root contains several compounds that promote sleep and reduce anxiety. These include valerenic acid, isovaleric acid, and a variety of antioxidants. Valerenic acid inhibits the breakdown of GABA in the brain, resulting in feelings of calmness and tranquility, how anti-anxiety medications like Valium and Xanax work. (10), (22)

CALM DOGS® VETERINARY FORMULA PROVIDES LONG TERM RELEIF FROM STRESS AND ANXIETY WITH AMINO ACIDS, VITAMINS, AND MINERALS NEEDED TO BALANCE NEUROTRANSMITTERS AND BRAIN CHEMISTRY NEUROTRANSMITTER PRECURSORS IN ANXIETY

A brief introduction:

[Low Serotonin] (whose precursor is the amino acid L-Tryptophan) can cause anxiety. Low GABA (gamma aminobutyric acid), whose main precursor is the amino acid L-Glutamine GABA (an inhibitory neurotransmitter) is our natural ‘valium.’ Low GABA causes anxiety. GABA can be supplemented directly. Low Dopamine (whose precursors are the amino acids L-Tyrosine and L-Phenylalanine) can cause anxiety. Elevated Norepinephrine and Epinephrine are associated with anxiety and panic disorders. Two other amino acids lower anxiety — taurine and l-theanine. 

We have in-depth research about the biochemistry of anxiety, and several different kinds of anxiety have been identified, including generalized anxiety disorder (GAD), panic disorder, phobic disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and separation anxiety disorder. 

AMINO ACIDS
L-Tryptophan

5-HTP – NATURE’S PROZAC. 5-HTP reduces the severity of anxiety.

L-Tryptophan and 5-HTP are widely used alternative treatments of generalized anxiety. Both amino acids are essential for the manufacture of serotonin in the brain. Serotonin is a neurotransmitter that plays a central role in regulating mood and anxiety. Research evidence supports the use of 5-HTP for anxiety. 5-HTP (5-Hydroxytryptophan) is a chemical by-product of the protein building block L-Tryptophan. It is also produced commercially from the seeds of an African plant known as Griffonia Simplicifolia. 5-HTP works in the brain and central nervous system by increasing the production of the chemical serotonin. Serotonin can affect sleep, appetite, temperature, sexual behavior, and pain sensation. Since 5-HTP increases the synthesis of serotonin, it is used for several conditions where serotonin is believed to play an important role such as anxiety, phobias, obsessive-compulsive behavior, depression, aggression, and impulse control problems. (11), (28)

5-HTP

Referred to as the “COOL” neurotransmitter, GABA (Gamma-Aminobutyric Acid) acts as a significant mood modulator by regulating the neurotransmitters noradrenaline, dopamine, and serotonin. GABA helps shift a tense, worried state to relaxation and a sad mood to a happy one. Reduced levels of GABA in the brain and nervous system are linked to anxiety, tension, and insomnia. Prescription tranquilizers like Valium and Xanax work by increasing the system’s response to GABA. In the mental health community, GABA is widely acknowledged for its ability to help regulate brain and nerve cell functioning, producing a calming and focusing effect. (12), (13)

GABA

L-Glutamine: Glutamate and GABA are primary excitatory and inhibitory neurotransmitters in the human brain, respectively. Evidence has shown that the central glutamate system plays a significant role in the pathogenesis of mood and anxiety disorders. Research shows that dysfunction of glutamate neurotransmission may be an early and primary pathology of stress-related disorders. Similarly, alterations in GABAergic neurotransmission have been implicated in depression and anxiety disorders, and positive GABA modulators have also been reported to have anxiolytic effects. L-Glutamine administration significantly increases ECF GABA concentrations and glutamate by 30%. Glutamatergic abnormality is related to depression as well as anxiety disorders. (14), (15)

L-Glutamine

L-Lysine: Dietary supplementation with the essential amino acid L-Lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-Lysine. It has been confirmed that amino acid treatment significantly reduced both trait anxiety and state anxiety induced by stress. L-Lysine also reduces basal levels of stress hormones. L-Lysine has been shown to act as a partial serotonin receptor 4 (5-HT4) antagonist, decreasing the brain-gut response to stress and decreasing blood cortisol levels. Based on the results from animal studies, two placebo-controlled studies were conducted to analyze the effects of L-Lysine and anxiety. The first of these clinical trials were conducted in healthy male volunteers who suffered from high-trait anxiety based on a STAI questionnaire. This study showed that L-Lysine supplements improved participants’ ability to handle induced stress through an increase in cortisol, while placebo had no reported improvement of anxiety symptoms. The second RCT recruited 108 healthy Japanese individuals. After one week of treatment with an oral L-Lysine, basal levels of salivary cortisol decreased in male subjects (n = 54). Supplementation also significantly reduced state anxiety (a temporary condition characterized by apprehension, tension, and fear about a specific situation or activity) and trait anxiety (a pre-set level of anxiety or a tendency to be anxious) in both males and females. (16), (17), (18)

L-Lysine

L-Theanine. This amino acid has sometimes been called “Zen in a bottle” for its unique ability to promote a sense of alert calmness. Theanine increases the calming neurotransmitter, GABA (Gamma-aminobutyric Acid) to induce the relaxed yet focused “alpha” state normally attained through meditation. As the active substance in green tea, one of the oldest calming mood-stabilizers known to man, theanine has been used for centuries to increase focus, concentration, learning, and memory, while providing a sense of “alert relaxation” and shutting off “worry” impulses. (21), (22)

L-Theanine

VITAMINS AND MINERALS FOR ANXIETY. Vitamin B1, B6, B12, Folic Acid, D3, and Magnesium

Vitamins and minerals serve as the co-factors for amino acid chemistry. B vitamins are our stress vitamins and are necessary for a healthy functioning nervous system. In terms of neurotransmitters involved in anxiety, we need vitamins B1, B6, B12, and Folic Acid.

B-Vitamins play a critical role in maintaining energy levels and work in close combination to influence vital body processes. Stress, exhaustion, and anxiety can drain the body of B vitamins as they are used up to manufacture stress hormones and neurotransmitters. In addition to delivering oxygen to the brain and protecting it from harmful oxidants. B-vitamins help convert glucose into energy for brain cells and keep neurotransmitters in circulation. B-vitamins also supports healthy nerve function and aid in calming over-reactive neurons from firing during times of emotional stress. (22)

Vitamin D. Research suggests vitamin D deficiency could be linked with anxiety disorders. For example, a 2015 review study reports that people with symptoms of anxiety or depression had lower calcidiol levels, a by-product of vitamin D breakdown, in their bodies. A 2017 study found that taking vitamin D supplements improved depression and anxiety. (20), (22)

Magnesium directly affects serotonin balance and helps keep us calm and relaxed. Studies have found that feelings of fear and panic can be significantly reduced with greater Magnesium intake. It is already known that Magnesium plays an essential role in the brain, most notably creating vital neurological pathways that ensure good communications between the brain and the body. Perhaps even more interesting, especially in terms of the potential magnesium-anxiety link, is the understanding that Magnesium also controls the hypothalamic-pituitary-adrenocortical (HPA) axis, which is the hub of the body’s stress response system. Could one of the symptoms of Magnesium deficiency be anxiety? Research suggests that taking Magnesium for anxiety can work well. Studies have found that feelings of fear and panic can be significantly reduced with greater Magnesium intake. The good news is that the results aren’t limited to generalized anxiety disorder. The magnesium-anxiety association also appears to be strong in terms of a PTSD Post-traumatic stress link. (19), (22)

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References

  1.  Direct evidence for GABAergic activity of withania somnifera on mammalian ionotropic GABAA and GABAp receptors. Journal of Ethnopharmacology. 2015 Aug 2;171:264-272. Doi:10.1016/j.jep.05.058. Epub 2015 June 9.
  2.  Avallone R, Zanoli P, Corsi L, Cannazza G, Baraldi M. Benzodiazepine compounds and GABA in flower heads of matricaria chamomilla. Phytotherapy Res. 1996; 10:177-179.
  3.  Mol Med Report. Author manuscript; available in PMC 2011 Feb 1. Published in final edited form as Mol Med Report. 2010 Nov 1; 3(6): 895-901. Doi: 10.3892/mmr.2010.377.
  4.  A systemic review and meta-analysis of the effect and safety of ginger in the treatment of nausea and vomiting. Nutr J. 2014; 13: 20. Published online 2014 Mar 19. doi: 10.1186/1475-2891-13-20.
  5. CNS Drugs. 2002;16(11):731-43. Therapeutic potential of kava in the treatment of anxiety disorders. https://www.ncbi.nlm.nih.gov/pubmed/12383029.
  6. Anti-Stress Effects of Lemon Balm, Nutrients. 2014 Nov; 6(11): 4805-4821. Published online 2014 030. doi: 10.3390/nu6114805.
  7. Hansen MV, Halladin NL, Rosenberg J, et al. Melatonin for pre-and postoperative anxiety. Cochrane Database of Systematic Reviews. 2015;(4):CD009861.
  8. Harvard Health LetterOmega-3’s for anxiety? News briefs Published: January 2019.
  9. Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26:369-373.
  10. GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology. 2009 Jan;56(1):174-81. doi: 10.1016/j.neuropharm.2008.06.013. Epub 2008 Jun 17.
  11. “Anxiety: The Integrative Mental Health Solution” by James Lake. http://theintegrativementalhealthsolution.com/anxiety-the-integrative-mental-health-solution.html The role of GABA in anxiety disorders. J Clin Psychiatry. 2003;64 Suppl 3:21-7.
  12. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat. 2015;11: 165-175. Published online 2015 Jan 17. doi: 10.2147/NDT.S58841
  13. Hasler, G., Buchmann, A., Haynes, M. et al. Association between prefrontal glutamine levels and neuroticism determined using proton magnetic resonance spectroscopy. Transl Psychiatry 9, 1970 (2019). 
  14. Modi, S. Rana, P., Kaur, P., Rani, N. & Khushu, S. Glutamate level in anterior cingulate predicts anxiety in healthy humans: a magnetic resonance spectroscopy study. Psychiatry Res. 224, 34-41 (2014).
  15. Smriga M, Torii K: L-lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci USA. 2003, 100: 15370-15375. 10.1073/pnas.2436556100.
  16. Srinongkote S, Smriga M, Nakagawa K, Toride Y: A diet fortified with L-lysine and L-arginine reduces plasma cortisol and blocks anxiogenic response to transportation in pigs. Nutr Neurosci. 2003, 6: 283-289. 10.1080/10284150310001614661.
  17. Jezova D, Makatsori A, Smriga M, Morinaga Y, Duncko R: Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety. Nutr Neurosci. 2005, 8: 155-160. 10.1080/10284150500162937.
  18. Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y: Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomed Res. 2007, 28: 85-90. 10.2220/biomedres.28.85.
  19. Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. Neuropharmacology. 2012 Jan; 62(1): 304-312. doi: 10.1016/j.neuropharm.2011.07.027.
  20. Vitamin D in Anxiety and Affective Disorders M. Bicikova, M. Duskova, J. Vitku, B. Kalvachova, D. Ripova, P. Mohr, L. Starka Institute of Endocrinology, Prague, Czech Republic, National Institute of Mental Health, Klecany, Czech Republic June 8, 2015.
  21. Psychotropic effects of L-theanine and its clinical properties: From the management of anxiety and stress to a potential use in schizophrenia. Lopes Sakamoto F, Metzker Pereira Ribeiro R, Amador Bueno A, Oliveira Santos H.Pharmacol Res. 2019 Sep;147:104395. doi: 10.1016/j.phrs.2019.104395. Epub 2019 Aug 11.PMID: 3142272 Review.
  22. Top 10 evidence-based supplements for anxiety, Carter, Berry, July 22, 2019, Medical News Today.
  23. An Alternative Treatment for Anxiety: A Systematic Review of Human Trial Results Reported for the Ayurvedic Herb Ashwagandha (Withania somnifera) J Altern Complement Med. 2014 Dec 1; 20(12): 901–908. doi: 10.1089/acm.2014.0177.
  24. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Benzie IFF, Wachtel-Galor S, editors. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.
  25. The Effects of Ginger Extract and Diazepam on Anxiety Reduction in Animal Model. Fatemeh Fadaki, Mehrdad Modaresi, Ilnaz Sajjadian. Department of Psychology, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, IRAN 2Department of Animal Science, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, IRAN.
  26. The effect of Melatonin on Depressive symptoms, Anxiety, Circadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial. Michael Tvilling Madsen, Anders Isbrand, Ulla Overgaard Andersen, Lars Juel Andersen, Mustafa Taskiran, Erik Simonsen, and Ismail Gogenur. Trials. 2017; 18: 81. Published online 2017 Feb 23. doi: 10.1186/s13063-017-1806-x.
  27. Omega 3 Consumption and Anxiety Disorders: A Cross-Sectional Analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Nutrients. 2018 Jun; 10(6): 663. Published online 2018 May 24. doi: 10.3390/nu10060663.
  28. Anxiety and 5-HTP. Roberta Lee MD, CaC, in Integrative Medicine (Fourth Edition), 2018.

CALM DOGS® VETERINARY FORMULA MAXIMUM STRENGTH CALMING AID