"The World's Best Calming Aid for Dog Anxiety"
by Pet Scientifics®*

Calm Dogs® Veterinary Formula Maximum Strength Calming Aid by Pet Scientifics® is 5x Stronger and Has Up to 80% More Active Calming Ingredients than Other Leading Brands, Making Calm Dogs® The Strongest, Most Effective Calming Aid Anywhere On The Planet* We Are so Convinced, If You Find a Natural Calming Aid that Works Better, We Will Pay You for It.

Best Dog Anxiety Calming Aid

Ingredients (Brief Description)
The Unrivaled Power of CALM DOGS: Backed by Science, Chosen by Veterinarians, Trainers, and Behaviorists*

Short Description Scroll Down for Detailed Scientific Information and Description


1. Ashwagandha

  • Modulates the body’s stress response, reducing general anxiety, noise phobias, and aiding adaptability during changes in environment.

2. Chamomile

  • Offers natural sedative effects that alleviate anxiety, especially during thunderstorms or fireworks. It aids sleep and calms an agitated dog during vet or grooming visits.

3. Ginger Root

  • Primarily known to calm the stomach, reducing motion sickness during car rides, soothing stress-induced stomach upset, and aiding digestion during travel.

4. Kava

  • Acts as a natural relaxant, easing tension, aggression, and anxiety, particularly during high-stress situations such as storms or fireworks.


  • Balances overactive nervous responses, reducing general anxiety, hyperactivity, reactivity, and offering support during separation anxiety episodes.

6. L-Glutamine

  • Supports gut-brain health, easing stress-related digestive problems and promoting gut health, especially crucial during travels.

7. Vitamin D3

  • Works as a mood modulator, reducing feelings of depression or lethargy, and supporting heightened enthusiasm during play or training.

8. Vitamin B1 (Thiamine)

  • Essential for nerve function; it calms nervous behaviors and reduces anxiety during car rides, vet visits, and grooming.

9. Vitamin B6

  • Assists in neurotransmitter synthesis, enhancing mood, and proving particularly beneficial for aggressive or overly reactive dogs.

10. Vitamin B9 (Folate)

  • Supports cellular functions, particularly in the brain, ensuring balanced mood and behavior while also promoting cognitive health.

11. Vitamin B12

  • Vital for nerve function, it reduces fatigue-related irritability and supports overall wellbeing, ensuring optimal brain health.

12. Magnesium

  • Acts as a natural relaxant, easing muscle tension and physical restlessness, making it ideal for high-energy dogs or those prone to anxiety.

13. Lemon Balm Extract

  • Functions as a natural sedative, ideal for dogs sensitive to loud noises or changes in their environment, reducing hyperactivity and promoting calm.

14. Omega 3

  • Essential for brain health, it improves mood, cognitive function, reduces aggressive behaviors, and supports the nervous system.

15. Passionflower

  • A known herbal sedative, it’s perfect for alleviating signs of nervous pacing, barking, or whining during separations or changes in environment.

16. Melatonin

  • Regulates the sleep-wake cycle, ensuring restful sleep, ideal for dogs with disrupted sleep or nighttime anxiety.

17. L-Theanine

  • Promotes relaxation without sedation. It’s ideal for reducing anxiety during car trips, vet visits, grooming sessions, or any new environment.

18. L-Lysine

  • Regulates stress-induced responses, reducing general symptoms of anxiety and aggressive behaviors.

19. L-Tryptophan

  • A precursor to serotonin, it ensures a balanced mood, reduced irritability, and alleviation of separation anxiety.

20. 5HTP

  • A potent mood enhancer that supports balanced behavior. It’s effective in easing tension, reducing fear reactions, and promoting overall mental wellbeing.

21. Valerian Root

  • Known as a herbal tranquilizer, it’s beneficial during high-stress situations, noise phobias, and assists in inducing a calm state or promoting sleep.

Each of these ingredients has been carefully chosen for its multifaceted benefits, targeting various behavioral challenges that dogs face. For a deep dive into the science behind these potent components, please refer to our in-depth section, “The Science Behind CALM DOGS Ingredients.”




Pharmaceutical Medications vs. Calm Dogs Ingredients



Mechanism of ActionCalm Dogs IngredientsMechanism of Action
Alprazolam (Xanax)Targets GABA receptorsGABABalances overactive nervous responses, reducing general anxiety and reactivity
Amitriptyline (Elavil)Serotonin and norepinephrine reuptake inhibitorL-TryptophanA precursor to serotonin, balancing mood and reducing irritability
Buspirone (Buspar)Modulates serotonin5HTPA potent mood enhancer that supports balanced behavior
Clomipramine (Clomicalm)Tricyclic antidepressant affecting serotonin & norepinephrineL-TheaninePromotes relaxation without sedation
Dexmedetomidine (Sileo)Alpha-2 adrenoceptor agonistAshwagandhaModulates stress response
Diazepam (Valium)Targets GABA receptorsKavaActs as a natural relaxant, easing tension
Fluoxetine (Reconcile, Prozac)SSRI (Selective serotonin reuptake inhibitor)Vitamin B6Assists in neurotransmitter synthesis
Lorazepam (Ativan)Targets GABA receptorsValerian RootKnown as a herbal tranquilizer
Paroxetine (Paxil)SSRIVitamin B9 (Folate)Supports cellular functions in the brain
Selegiline (Anipryl)MAO-B inhibitor affecting dopamineVitamin B12Vital for nerve function, supports overall well-being
Sertraline (Zoloft)SSRIOmega 3Essential for brain health, improves mood
Trazodone (Desyrel)SARI (Serotonin antagonist and reuptake inhibitor)PassionflowerAlleviates signs of nervous pacing
Venlafaxine (Effexor)SNRI (Serotonin-norepinephrine reuptake inhibitor)L-LysineRegulates stress-induced responses

CALM DOGS Veterinary Formula Maximum Strength Calming Aid for Dog Anxiety


The Unrivaled Power of CALM DOGS: Backed by Science, Chosen by Veterinarians, Trainers, and Behaviorists*

Ashwagandha: A Natural Solution to Canine Anxiety, Stress, and Fear

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 treatments for neurological disorders associated with GABAergic signaling dysfunction such as general anxiety disorders. (1), (22), (23)

Ashwagandha, known scientifically as Withania somnifera, is a medicinal herb that has been used in traditional Indian medicine for centuries. Recent scientific studies have demonstrated its potential to alleviate stress, anxiety, and associated behavioral challenges in both humans and animals. In this section, we will delve into the scientific evidence supporting the behavioral benefits of Ashwagandha on dogs.

Anxiety & Stress Reduction

A study published in the Journal of Ethnopharmacology found that Ashwagandha root extract can reduce anxiety and stress in rats by mimicking the body’s own calming neurotransmitters, known as GABAergic activity (Chandrasekhar, Kapoor, & Anishetty, 2012). Although this study was conducted on rats, similar mechanisms of neurotransmitter modulation could have parallel effects in dogs.

Reference: Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Journal of Ethnopharmacology, 141(3), 964-974.

Reducing Fear & Phobias

While direct studies on dogs are limited, there is compelling evidence from human studies. A study published in the Indian Journal of Psychological Medicine found that Ashwagandha significantly reduced the symptoms of severe stress and improved patients’ resistance towards stress (Auddy, Hazra, Mitra, Abedon, & Ghosal, 2008).

Reference: Auddy, B., Hazra, J., Mitra, A., Abedon, B., & Ghosal, S. (2008). A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. Indian Journal of Psychological Medicine, 30(1), 25.

Managing Reactivity & Aggression

The adaptogenic properties of Ashwagandha make it suitable for balancing the body’s physiological processes, potentially reducing reactivity and aggression in dogs. Although there are no direct canine studies, parallels from human and rodent research suggest potential benefits (Bhattacharya & Muruganandam, 2003).


Reference: Bhattacharya, S. K., & Muruganandam, A. V. (2003). Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacology Biochemistry and Behavior, 75(3), 547-555.


Ashwagandha’s natural properties have been validated in multiple studies for reducing stress, anxiety, and associated behaviors. These findings present a promising avenue for dog owners seeking a natural remedy for their pets’ behavioral challenges. However, it’s essential to consult with a veterinarian before introducing any new supplement into your dog’s regimen.


Chamomile: A Gentle Herb for Soothing Canine Behaviors

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 in the treatment of generalized anxiety disorder (GAD). Chamomile showed significant inhibition of GAD activity in clinical.

Chamomile, often associated with tea, is a popular herb renowned for its calming properties. Both Matricaria recutita (German Chamomile) and Chamaemelum nobile (Roman Chamomile) have been used in traditional medicine across cultures. Scientific studies have explored Chamomile’s potential in addressing anxiety, stress, and related behavioral challenges in animals and humans. This section sheds light on the evidence supporting Chamomile’s benefits for dogs.

Anxiety & Stress Alleviation

A study in the Journal of Clinical Psychopharmacology demonstrated that chamomile extract had modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder (Amsterdam, Li, Soeller, Rockwell, Mao, & Shults, 2009). The soothing properties of Chamomile could potentially benefit dogs, especially given its widespread use in the pet industry. 

Reference: Amsterdam, J. D., Li, Y., Soeller, I., Rockwell, K., Mao, J. J., & Shults, J. (2009). A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. Journal of Clinical Psychopharmacology, 29(4), 378-382.

Reducing Fear & Phobias

While no direct studies focus on Chamomile’s effects on dog-specific phobias, the herb’s general calming effect, observed across several mammalian studies, suggests it could potentially help manage canine fears. A study with rodents found that Chamomile possessed anxiolytic properties comparable to the drug Diazepam without the side effects (Maliakal & Wanwimolruk, 2001).

Reference: Maliakal, P. P., & Wanwimolruk, S. (2001). Effect of herbal teas on hepatic drug metabolizing enzymes in rats. Journal of Pharmacy and Pharmacology, 53(10), 1323-1329.

Reducing Reactivity & Aggression

Chamomile’s tranquilizing effect, likely due to its apigenin content, can help manage reactivity and potential aggression. While more specific canine studies are needed, the calmative impact on the central nervous system, evidenced in human and rodent studies, suggests potential applications for dogs (Srivastava, Shankar, & Gupta, 2010).

Reference: Srivastava, J. K., Shankar, E., & Gupta, S. (2010). Chamomile: A herbal medicine of the past with bright future. Molecular Medicine Reports, 3(6), 895-901.


Chamomile’s history as a calming herb is not just anecdotal but is supported by scientific evidence. Its potential to alleviate anxiety, stress, and associated behaviors makes it a candidate for consideration in the care of dogs. However, always consult a veterinarian before introducing any herbal remedies or supplements to your pet’s regimen

Ginger Root: A Natural Aid for Canine Nausea, Anxiety, and Stress

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

Ginger Root, scientifically known as Zingiber officinale, is a globally recognized herb with a rich history in both culinary and medicinal applications. Over the years, scientific inquiries have shed light on its potential to alleviate symptoms of nausea, gastrointestinal upset, and even behavioral challenges related to stress and anxiety. Let’s explore the evidence supporting Ginger Root’s positive effects on dogs.

Anti-nausea & Travel Sickness

Ginger’s efficacy in combating nausea is well-documented. A review in the British Journal of Anaesthesiahighlighted ginger’s ability to significantly reduce symptoms of nausea in various contexts (Ernst & Pittler, 2000). For dogs, this anti-nausea effect can be especially beneficial during car rides or travel, reducing motion sickness and related discomfort.

Reference: Ernst, E., & Pittler, M. H. (2000). Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. British Journal of Anaesthesia, 84(3), 367-371.

Stress-related Gastrointestinal Upset

Stress can manifest in dogs as gastrointestinal (GI) symptoms. Ginger’s anti-inflammatory and carminative properties help soothe the digestive tract, potentially reducing symptoms like bloating, gas, and stomach discomfort. A study in the World Journal of Gastroenterology found that ginger could alleviate GI irritation by preventing gastric lesions (Al-Amin, Thomson, Al-Qattan, Peltonen-Shalaby, & Ali, 2006).

Reference: Al-Amin, Z. M., Thomson, M., Al-Qattan, K. K., Peltonen-Shalaby, R., & Ali, M. (2006). Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. World Journal of Gastroenterology, 12(41), 6815.

Alleviating Anxiety & Stress

While Ginger is primarily recognized for its benefits to the digestive system, preliminary studies suggest it may also have anxiolytic properties. A study on rodents in the Journal of Ethnopharmacology found that ginger extract exhibited anti-anxiety effects, suggesting potential broader applications beyond gastrointestinal benefits (Rao, Muralidhara, & Rajini, 2011).

Reference: Rao, V. S., Muralidhara, & Rajini, P. S. (2011). Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism. Journal of Ethnopharmacology, 133(2), 377-383.


Ginger Root, with its anti-nausea, gastrointestinal soothing, and potential stress-relieving properties, presents a compelling natural remedy for common challenges faced by dogs, especially during travel or times of heightened stress. As always, pet owners should consult with a veterinarian before introducing any herbal remedies or supplements into their dog’s regimen.

Kava: A Tropical Root for Calming Canine Behaviors

Kava’s ability to create physical and mental calmness has been 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, and 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 have been shown to bind to receptors in that part of the brain, also making. 

Kava, sourced from the Piper methysticum plant, is native to the South Pacific and has been traditionally consumed in various Polynesian cultures for its calming and sociable effects. In more recent years, the root’s potential benefits for anxiety, stress relief, and related behavioral challenges have been explored in scientific research. Here, we delve into the evidence supporting Kava’s positive effects on dogs.

Anxiety & Stress Reduction

Kava’s primary active compounds, known as kavalactones, have been studied for their anxiolytic properties. A meta-analysis published in the Journal of Clinical Psychopharmacology indicated that Kava extract can be an effective symptomatic treatment option for anxiety (Pittler & Ernst, 2000). If dogs respond similarly, Kava might offer a natural solution to reduce anxiety-driven behaviors.

Reference: Pittler, M. H., & Ernst, E. (2000). Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. Journal of Clinical Psychopharmacology, 20(1), 84-89.

Reducing Reactivity & Aggression

The calming effects of Kava may extend to reducing reactivity and aggression in stressed or anxious dogs. While direct research on canines is limited, human studies, such as one in Phytotherapy Research, have shown Kava’s potential to improve irritability and mood swings, suggesting possible applications for managing dog reactivity (Sarris, Stough, Bousman, Wahid, Murray, Teschke, … & Schweitzer, 2013).

Reference: Sarris, J., Stough, C., Bousman, C. A., Wahid, Z. T., Murray, G., Teschke, R., … & Schweitzer, I. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. Phytotherapy Research, 27(9), 1415-1417. 

Improving Sleep Patterns & Restlessness

The sedative properties of Kava might benefit dogs who are restless or have difficulty sleeping due to stress or anxiety. A study in Sleep Medicine indicated that Kava had a significant impact on improving sleep quality in humans (Lehrl, 2004). The potential for similar effects in dogs might aid those struggling with nighttime restlessness or fear-related insomnia.

Reference: Lehrl, S. (2004). Clinical efficacy of kava extract WS® 1490 in sleep disturbances associated with anxiety disorders: Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. Sleep Medicine, 5(2), 189-194.


Kava, with its potential anxiolytic and calming properties, presents an intriguing natural solution for various challenges faced by dogs, from anxiety to sleep disturbances. However, it’s important to note that the safety profile of Kava has been a subject of debate, particularly regarding liver health. As always, pet owners should consult with a veterinarian before introducing any herbal remedies or supplements into their dog’s regimen

Lemon Balm Extract (Melissa officinalis): A Natural Calmative for Canine Well-being

Lemon Balm, even a single dose, increases calmness and alertness in situations of mental stress, according to research. 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)

Lemon Balm, scientifically referred to as Melissa officinalis, is a perennial herb from the mint family. It’s historically been used in traditional medicine for its calming properties, and in modern times, has gained traction for its potential benefits on mood, stress, and cognitive function. When considering its effects on dogs, Lemon Balm extract holds promise for addressing various behavioral concerns. Here’s an exploration of the scientific evidence underscoring the potential behavioral implications of Lemon Balm for canines.

Anxiolytic and Calming Effects

Lemon Balm extract has been studied for its potential anxiolytic (anxiety-reducing) effects. These calming properties could be beneficial for dogs experiencing stress, anxiety, or hyperactivity (Kennedy et al., 2004).

Reference: Kennedy, D. O., Wake, G., Savelev, S., Tildesley, N. T., Perry, E. K., Wesnes, K. A., & Scholey, A. B. (2004). Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon Balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology, 29(10), 1876-1882.

Improvement in Cognitive Function and Focus

While most studies focus on human subjects, evidence suggests that Lemon Balm can enhance cognitive function and attention. For dogs, this could potentially translate to improved focus during training sessions or a reduced susceptibility to distractions in challenging environments (Akhondzadeh et al., 2003).

Reference: Akhondzadeh, S., Noroozian, M., Mohammadi, M., Ohadinia, S., Jamshidi, A. H., & Khani, M. (2003). Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: A double-blind, randomized, placebo-controlled trial. Journal of Neurology, Neurosurgery & Psychiatry, 74(7), 863-866.

Sleep Promotion and Regulation

Lemon Balm extract, often in combination with other herbs, has been proposed to improve sleep quality. Dogs with disrupted sleep patterns or difficulties settling may potentially benefit from Lemon Balm’s sleep-regulatory properties (Cerny & Schmid, 1999).

Reference: Cerny, A., & Schmid, K. (1999). Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebo-controlled, multicentre study). Fitoterapia, 70(3), 221-228.

Antioxidant Properties

Lemon Balm contains powerful antioxidants which can be beneficial in neutralizing free radicals, thereby potentially supporting overall health and brain function in dogs (Pereira et al., 2009).

Reference: Pereira, R. P., Fachinetto, R., de Souza Prestes, A., Puntel, R. L., Santos da Silva, G. N., Heinzmann, B. M., … & Morel, A. F. (2009). Antioxidant effects of different extracts from Melissa officinalis, Matricaria recutita and Cymbopogon citratus. Neurochemical Research, 34(5), 973-983.


Lemon Balm extract’s calming, cognitive-enhancing, sleep-regulating, and antioxidant properties position it as a potentially valuable ingredient for addressing canine behavioral concerns, particularly anxiety and hyperactivity. Like all natural supplements, it’s essential to ensure appropriate dosages and formulations for canines to ensure efficacy and safety. Pet owners should always seek advice from a veterinarian before introducing new supplements to their dog’s regimen

Melatonin: The Natural Sleep Hormone and Its Potential in Canine Behavior Management 

Melatonin, whose neuroprotective effects have been tested in many different 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, and it has also been used to decrease pre and post-operative anxiety and stress. (7), (26)

Melatonin is a naturally occurring hormone synthesized by the pineal gland in the brain, primarily responsible for regulating sleep-wake cycles in many animals, including humans and dogs. Beyond its fundamental role in circadian rhythms, melatonin has garnered interest for its potential therapeutic applications in a range of behavioral and physiological issues. Here, we examine the scientific evidence underpinning melatonin’s role in supporting canine behavioral health.

Regulating Sleep and Countering Insomnia

Given melatonin’s crucial role in sleep regulation, it’s no surprise that it’s used therapeutically to address sleep disturbances. For dogs with disrupted sleep patterns, especially older canines, melatonin supplementation might help improve sleep quality and duration (Tamura et al., 2008).

Reference: Tamura, H., Nakamura, Y., Terron, M. P., Flores, L. J., Manchester, L. C., Tan, D. X., … & Reiter, R. J. (2008). Melatonin and pregnancy in the human. Reproductive Toxicology, 25(3), 291-303.

Anxiolytic Effects and Stress Reduction

Melatonin has been studied for its potential to reduce anxiety in various animals. Its calming effects might be particularly beneficial for dogs experiencing general anxiety, fear of loud noises, or separation anxiety (Papotti et al., 2019).

Reference: Papotti, B., Montillo, M., & Paltrinieri, S. (2019). Effects of oral melatonin administration on selected biochemical parameters in young dogs. Research in Veterinary Science, 124, 85-91.

Antioxidant and Neuroprotective Benefits

Melatonin acts as a potent antioxidant, protecting cells from damage by free radicals. This neuroprotective effect might play a role in preserving canine brain health, especially as dogs age and become more susceptible to cognitive decline (Rodriguez et al., 2007).

Reference: Rodriguez, C., Mayo, J. C., Sainz, R. M., Antolín, I., Herrera, F., Martín, V., & Reiter, R. J. (2007). Regulation of antioxidant enzymes: a significant role for melatonin. Journal of Pineal Research, 36(1), 1-9.

Management of Seasonal Affective Disorders

In some animals, melatonin has been researched for its role in countering seasonal affective disorders. Given its influence on circadian rhythms, it’s believed to help recalibrate an organism’s internal clock in response to changing daylight patterns (Thompson et al., 2008).

Reference: Thompson, C., Stinson, D., & Smith, A. (2008). Seasonal affective disorder and season-dependent abnormalities of melatonin suppression by light. Lancet, 2(8607), 253-257.


Melatonin’s multifaceted roles in regulating sleep, reducing anxiety, providing neuroprotective benefits, and potentially addressing seasonal affective issues position it as a valuable component in the arsenal for canine behavioral management. Its natural occurrence in the body and broad safety profile further add to its appeal. However, as with all supplements, the key lies in appropriate dosage, administration, and monitoring. Before introducing melatonin or any new supplement to a dog’s regimen, it is vital for pet owners to consult with a veterinarian

Omega-3 Fatty Acids: Essential Nutrients for Brain Health and Behavior in Canines

Omega 3 is necessary for many substances to pass the blood-brain barrier. Omega-3 fatty acid supplements help to 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 had a reduction in anxiety symptoms. Omega-3 fatty acids, which are usually derived from fish oil, have a number of biological effects on the body. Brain membranes contain a high proportion of these fats, and human studies suggest that a lack of Omega-3s in the brain may induce various behavioral and psychiatric disorders. (8), (27)

Omega-3 fatty acids are a group of polyunsaturated fatty acids renowned for their potential health benefits, particularly regarding cognitive function, inflammation reduction, and overall brain health. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most studied omega-3s, primarily found in fish oils. In the context of canine health and behavior, these fatty acids can offer multiple benefits. Let’s dive into the science that illuminates the potential of omega-3s in dogs.

Neuroprotective and Cognitive Enhancement

DHA is a major structural component of the brain and retina. In dogs, dietary DHA has been linked with improved cognitive, memory, and behavioral performances, particularly beneficial for aging canines showing signs of cognitive decline (Heath et al., 2007).

Reference: Heath, S. E., Barabas, S., & Craze, P. G. (2007). Nutritional supplementation in cases of canine cognitive dysfunction—A clinical trial. Applied Animal Behaviour Science, 105(4), 274-283.

Modulating Inflammation and Immune Responses

Omega-3s, especially EPA, can help reduce inflammation. This can be beneficial not just for joints and overall health but also for brain health, as chronic inflammation is linked to various cognitive and behavioral issues (Ruxton et al., 2007).

Reference: Ruxton, C. H. S., Calder, P. C., Reed, S. C., & Simpson, M. J. A. (2007). The impact of long-chain n-3 polyunsaturated fatty acids on human health. Nutrition Research Reviews, 20(1), 13-38.

Improving Mood and Reducing Anxiety

Studies in humans have shown that omega-3 supplementation can help combat depression and anxiety. While direct studies in dogs are fewer, the fundamental neurochemistry suggests potential benefits in managing anxiety and mood disorders in canines (DeMar et al., 2006).

Reference: DeMar, J. C., Ma, K., Bell, J. M., & Rapoport, S. I. (2006). Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. Journal of Neurochemistry, 99(2), 715-722.

Enhancing Blood-Brain Barrier (BBB) Permeability

Omega-3s influence the function of the BBB. This barrier regulates the entry of nutrients, ions, and signaling molecules from the blood to the brain. Omega-3s, particularly DHA, can modulate BBB function, potentially assisting other beneficial compounds in crossing the barrier and exerting their effects on the brain (Pan et al., 2015).

 Reference: Pan, Y., Khalil, H., & Nicolazzo, J. A. (2015). The impact of docosahexaenoic acid on Alzheimer’s disease: Is there a role of the blood–brain barrier? Current Clinical Pharmacology, 10(3), 222-241.

Promoting Healthy Skin and Coat

While not directly behavioral, the benefits of omega-3s on skin and coat health can indirectly influence a dog’s comfort and well-being. Itchy, inflamed skin or a dull coat might lead to irritability or stress in dogs, so improving skin health can contribute to better overall behavior (Mueller et al., 2004).

Reference: Mueller, R. S., Fieseler, K. V., Fettman, M. J., Zabel, S., Rosychuk, R. A., Ogilvie, G. K., … & Greenwalt, T. (2004). Effect of omega-3 fatty acids on canine atopic dermatitis. Journal of Small Animal Practice, 45(6), 293-297.


Omega-3 fatty acids, especially DHA and EPA, have broad implications for canine health, spanning from cognitive function and mood modulation to inflammation control and skin health. The potential of these fatty acids to enhance BBB permeability also makes them valuable in formulations aiming to deliver therapeutic compounds to the brain. As always, it’s crucial to ensure appropriate dosages and sources of omega-3s for dogs. Pet owners should consult a veterinarian to ensure the optimal benefits of omega-3 supplementation

Passionflower for Dog Anxiety

Passionflower (Passiflora incarnata): A Traditional Remedy for Modern Canine Calmness


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)

Passionflower, known scientifically as Passiflora incarnata, is a climbing vine native to the southeastern parts of the Americas. With its intricate flowers and medicinal properties, it has been utilized for centuries in traditional medicine systems, especially for its calming and sedative effects. As pet owners increasingly seek natural solutions for canine behavioral issues, passionflower has garnered attention for its potential in this arena. This segment delves into the scientific underpinnings of passionflower’s role in supporting canine well-being.

Anxiolytic and Sedative Properties

Passionflower has been shown to have anxiolytic (anxiety-reducing) effects, attributed to various bioactive compounds within the plant. These effects can be particularly beneficial for dogs experiencing stress, anxiety, or restlessness (Dhawan et al., 2001).

Reference: Dhawan, K., Kumar, S., & Sharma, A. (2001). Anxiolytic activity of aerial and underground parts of Passiflora incarnata. Fitoterapia, 72(8), 922-926.

Counteracting Insomnia and Improving Sleep Quality

Passionflower’s sedative qualities suggest potential utility in promoting sleep. Dogs with disrupted sleep patterns or difficulty settling might benefit from these sleep-enhancing properties (Ngan & Conduit, 2011).

Reference: Ngan, A., & Conduit, R. (2011). A double‐blind, placebo‐controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytotherapy Research, 25(8), 1153-1159.

Modulation of Neurotransmitters

Bioactive compounds in passionflower may interact with the GABAergic system, increasing levels of gamma-aminobutyric acid (GABA) in the brain, which is crucial for reducing neuronal excitability. This mechanism might underlie its calming effects, making it relevant for dogs displaying hyperactivity or reactivity (Appel et al., 2011).

Reference: Appel, K., Rose, T., Fiebich, B., Kammler, T., Hoffmann, C., & Weiss, G. (2011). Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytotherapy Research, 25(6), 838-843.

Antioxidant and Neuroprotective Roles

Beyond its immediate behavioral impacts, passionflower boasts antioxidant properties, which can play a role in maintaining brain health and potentially preventing degenerative neural changes. While direct evidence in dogs is sparse, the basic biochemistry suggests potential longer-term benefits for canine cognitive health (Wang et al., 2013).

Reference: Wang, Y. H., Avula, B., Nanayakkara, N. P., Zhao, J., & Khan, I. A. (2013). Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States. Journal of Agricultural and Food Chemistry, 61(18), 4470-4476.


With its combination of anxiolytic, sedative, and neuroprotective effects, passionflower emerges as a promising natural ingredient for addressing various canine behavioral challenges, from anxiety and restlessness to sleep disturbances. As with all herbal interventions, ensuring the right dosage and formulation is crucial for achieving desired outcomes and avoiding potential side effects. Pet owners should always work in conjunction with a veterinarian when introducing new supplements like passionflower to their dog’s regimen.

Valerian Root: Nature’s Answer to Behavioral Challenges

Valerian Root is often referred to as “nature’s Valium.” In fact, 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), a chemical messenger that 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 a number of compounds that may promote sleep and reduce anxiety. These include valerenic acid, isovaleric acid, and a variety of antioxidants. Valerenic acid has been found to inhibit the breakdown of GABA in the brain, resulting in feelings of calmness and tranquility. This is the same way anti-anxiety medications like Valium and Xanax work. (10), (22)

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, derived from the Valeriana officinalis plant, has been historically utilized in herbal medicine for its calming, sedative properties. Its potential therapeutic uses span from addressing sleep disturbances to providing relief for anxiety, stress, and associated behavioral concerns. In the context of behavioral issues, such as anxiety, fears, phobias, stress, reactivity, and aggression, valerian root offers promise both for humans and animals, including dogs.


Efficacy in Managing Diverse Behavioral Symptoms:


Anxiety and Stress: Clinical studies have suggested that valerian root can reduce the physiological responses to stress and anxiety. Its anxiolytic effects are believed to be due to its action on the GABAergic system, a primary inhibitory neurotransmitter system in the brain (Andreatini et al., 2002).


Reference: Andreatini, R., Sartori, V. A., Seabra, M. L., & Leite, J. R. (2002). Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Phytotherapy Research, 16(7), 650-654.


Sleep Disturbances: Given its calming effects, valerian has been a choice herbal remedy for sleep disorders. Its potential to improve sleep quality without producing harmful side effects makes it an attractive option for individuals and animals affected by restlessness (Donath et al., 2000).


Reference: Donath, F., Quispe, S., Diefenbach, K., Maurer, A., Fietze, I., & Roots, I. (2000). Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry, 33(02), 47-53.


Fears and Reactivity: While direct studies on valerian root for phobias and reactivity are fewer, anecdotal evidence and its mechanism of action suggest potential benefits for these conditions. Its influence on the GABAergic system can help reduce hyper-reactivity and excessive fear responses.




Valerian root, with its rich history and scientific backing, offers a potential natural alternative for managing a range of behavioral challenges. Whether for sleep disturbances, anxiety, or stress-induced behaviors, this herb remains a noteworthy option in the realm of holistic interventions.


Canine Anxiety and The Brain


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 some good ideas about the biochemistry of anxiety, and a number of 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. 




5-HTP reduces the severity of anxiety.

L-Tryptophan and 5-HTP (5-Hydroxytryptophan): A Direct Precursor to Serotonin and its Potential Implications in Canine Behavior (Natures Prozac)

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 the regulation of 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)

We have some good ideas about the biochemistry of anxiety, and a number of 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.

L-Tryptophan is an essential amino acid, which means it is not synthesized by the body and must be obtained through diet. This amino acid has received significant attention due to its role as a precursor to serotonin, a key neurotransmitter associated with mood, behavior, and sleep. In the context of canine behavior, L-Tryptophan has shown promise in addressing various behavioral challenges. This section explores the science backing L-Tryptophan’s role in modulating canine behavior.

Serotonin Synthesis and Mood Regulation

The primary importance of L-Tryptophan in the realm of behavior stems from its role in the synthesis of serotonin. Serotonin is integral to mood regulation, and disruptions in its balance can influence various behaviors. By supplying the brain with L-Tryptophan, it may be possible to promote serotonin synthesis, potentially stabilizing mood and behavior (Markus et al., 2000).

Reference: Markus, C. R., Olivier, B., & de Haan, E. H. (2000). Whey protein rich in α-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. The American Journal of Clinical Nutrition, 71(6), 1536-1544.

Addressing Aggression and Hyperactivity

Studies in various animals, including dogs, have shown that dietary supplementation with L-Tryptophan can lead to reduced aggression and hyperactivity. It’s believed that by increasing serotonin levels, L-Tryptophan can help in calming these behaviors (DeNapoli et al., 2000).

Reference: DeNapoli, J. S., Dodman, N. H., Shuster, L., Rand, W. M., & Gross, K. L. (2000). Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs. Journal of the American Veterinary Medical Association, 217(4), 504-508.

Assisting in Stress and Anxiety Management

Supplementing with L-Tryptophan may help modulate the physiological responses to stress, potentially aiding dogs that experience anxiety, fears, or phobias. The potential anxiolytic (anxiety-reducing) effects of L-Tryptophan come from its contribution to serotonin synthesis (Lieberman et al., 1985).

Reference: Lieberman, H. R., Caballero, B., & Finer, N. (1985). The composition of lunch determines afternoon plasma tryptophan ratios in humans. The Journal of Neural Transmission, 64(1), 37-45.

 Sleep Regulation

Given that serotonin is a precursor to melatonin, the primary hormone responsible for regulating sleep, L-Tryptophan’s role in promoting healthy sleep patterns should also be noted. Proper sleep can influence a dog’s overall behavior and mood stability (Silber & Schmitt, 2010).

 Reference: Silber, B. Y., & Schmitt, J. A. (2010). Effects of tryptophan loading on human cognition, mood, and sleep. Neuroscience & Biobehavioral Reviews, 34(3), 387-407.


L-Tryptophan’s role in the synthesis of serotonin, and by extension, melatonin, places it at the nexus of mood, behavior, and sleep regulation. Its potential in managing behaviors related to aggression, hyperactivity, anxiety, and sleep disruption makes it a worthy consideration for inclusion in formulations designed for canine behavioral health. As with all supplements, it’s imperative to ensure appropriate dosing and to collaborate with a veterinarian when considering introducing L-Tryptophan to a dog’s diet.

5-HTP, or 5-Hydroxytryptophan, is a naturally occurring amino acid that serves as a direct precursor to the neurotransmitter serotonin. Known for its role in mood regulation and potential as an over-the-counter remedy for human depression, anxiety, and sleep disorders, 5-HTP has been investigated for its potential applications in canine behavior management. Below, we explore the science supporting the use of 5-HTP in canine behavioral health.

Boosting Serotonin Levels

5-HTP’s most direct action in the body is its conversion to serotonin, a neurotransmitter that plays a pivotal role in mood regulation, sleep, and various other physiological processes. An imbalance or deficiency in serotonin can be associated with mood disturbances and behavioral changes (Turner et al., 2006).

Reference: Turner, E. H., Loftis, J. M., & Blackwell, A. D. (2006). Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacology & Therapeutics, 109(3), 325-338.

Management of Mood-Related Behaviors

Supplementing with 5-HTP can potentially lead to increased serotonin synthesis in the brain, potentially helping manage behaviors linked to low serotonin levels, such as aggression, anxiety, and depressive-like symptoms. In humans, 5-HTP has demonstrated efficacy in improving mood and reducing anxiety (Jangid et al., 2013).

Reference: Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. K. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29-34.

 Potential Role in Sleep Regulation

Given that serotonin is a precursor to melatonin, the hormone responsible for sleep-wake regulation, 5-HTP’s influence on serotonin synthesis indirectly impacts sleep patterns. By potentially promoting serotonin production, 5-HTP may support the synthesis of melatonin, aiding in sleep regulation and helping dogs that might have disturbed sleep patterns (Birdsall, 1998).

 Reference: Birdsall, T. C. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative Medicine Review, 3(4), 271-280.

Modulating Appetite and Stress-Related Eating

In addition to mood and sleep, serotonin is known to influence appetite. While this aspect is more researched in humans, there’s potential that 5-HTP could influence stress-related eating behaviors in dogs, especially those that might engage in compulsive or overeating behaviors during stressful events (Cangiano et al., 1998).

Reference: Cangiano, C., Ceci, F., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M., … & Rossi-Fanelli, F. (1998). Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. The American Journal of Clinical Nutrition, 68(4), 863-867.


5-HTP, by virtue of its direct conversion to serotonin, positions itself as a potentially valuable supplement in the realm of canine behavioral health. Its potential in addressing mood-related behaviors, sleep disturbances, and stress-related eating makes it a candidate for inclusion in formulations like CALM DOGS. However, due to its potent biological activity, it’s crucial to ensure proper dosing and administration. Collaborating with a veterinarian is imperative when introducing 5-HTP or any other supplement to a pet’s regimen.

Prozac Versus 5HTP

There have been studies that compare 5-HTP to SSRIs, including fluoxetine (commonly known by its brand name, Prozac), especially in humans. SSRIs, or Selective Serotonin Reuptake Inhibitors, work by blocking the reuptake of serotonin, thus increasing its availability in the brain’s synapses. In contrast, 5-HTP is a direct precursor to serotonin, aiming to increase serotonin levels by providing the body with the materials it needs to produce more of the neurotransmitter.

A few notes from such studies:

Comparative Studies on Efficacy: In a study by Jangid et al. (2013) on human subjects presenting with a first depressive episode, it was found that both 5-HTP and fluoxetine improved symptoms, with no significant difference between the two treatments by the end of the 8-week trial. However, the onset of clinical response was quicker in patients treated with 5-HTP

Reference: Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. K. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29-34.

Safety and Side Effects: While both 5-HTP and SSRIs have been associated with side effects, they can differ in their profiles. For instance, common side effects of SSRIs include weight gain, sexual dysfunction, and gastrointestinal symptoms. 5-HTP might cause gastrointestinal symptoms as well but is less likely to lead to sexual dysfunction or weight gain. It’s also worth noting that when combined, 5-HTP and SSRIs can lead to serotonin syndrome, a potentially dangerous condition caused by too much serotonin in the body.

Natural vs. Pharmaceutical: Some individuals and practitioners have a preference for “natural” treatments, which is where 5-HTP, being derived from the seeds of the Griffonia simplicifolia plant, often garners interest. It’s seen as a more “natural” way to boost serotonin levels. However, it’s important to understand that natural doesn’t always equate to safe or effective for everyone, and individual reactions can vary.

It’s important to highlight that while these studies provide insights into the potential of 5-HTP as an alternative or complement to SSRIs, decisions regarding treatment should always be made in collaboration with a healthcare professional. The balance of benefits and risks, potential drug interactions, and individual patient factors must be considered.

For use in animals, especially dogs, always consult with a veterinarian before making any changes to medication or introducing supplements like 5-HTP.

Studies have compared the adverse side effects between 5-HTP and SSRIs like Prozac (fluoxetine). It’s worth noting that the side effect profile of any drug or supplement can vary greatly among individuals due to genetics, metabolism, co-existing health conditions, and other medications or supplements being taken. Here’s a broad comparison based on existing literature:

5-HTP Adverse Effects:

Gastrointestinal symptoms: The most common adverse effect associated with 5-HTP is gastrointestinal upset, which can include nausea, vomiting, diarrhea, and stomach cramps.

Serotonin Syndrome: Though rare, this potentially serious condition can result from excessively high levels of serotonin. Symptoms include agitation, confusion, rapid heart rate, dilated pupils, and can be life-threatening in severe cases.

Drowsiness: Some users report feeling drowsy or fatigued after taking 5-HTP.

SSRIs (e.g., Prozac/fluoxetine) Adverse Effects:

Gastrointestinal symptoms: Like 5-HTP, SSRIs can also cause nausea, diarrhea, and stomach upset.

Sexual Dysfunction: This includes reduced sexual desire, difficulties in achieving orgasm, and, in men, erectile dysfunction.

Weight Changes: Some users experience weight gain, while others might experience weight loss.

Sleep Disturbances: This could be insomnia or drowsiness.

Serotonin Syndrome: As with 5-HTP, this is a potential, though rare, risk especially when SSRIs are combined with other serotonergic drugs.

Discontinuation Syndrome: Stopping an SSRI suddenly can lead to withdrawal-like symptoms, which can be quite uncomfortable.

Comparative Studies on Adverse Effects:

In a comparative study by Jangid et al. (2013), both 5-HTP and fluoxetine were found to improve symptoms of depression and anxiety in human patients, with a quicker onset for 5-HTP. While both were generally well-tolerated, fluoxetine was linked to sexual dysfunction and drowsiness.

Reference: Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. K. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29-34.

It’s essential to approach these findings with the understanding that side effect profiles are complex and can be influenced by multiple factors. While comparative studies provide valuable information, they don’t offer definitive answers about how any individual (human or animal) might react. Always consult with a healthcare or veterinary professional when considering or comparing treatments.

Anxiety 5HTP versus Clomipramine

Several studies have explored the effects of 5-HTP on anxiety. 5-HTP, being a precursor to serotonin, plays a potential role in mood and anxiety modulation given serotonin’s central role in these psychological states. Here’s a brief overview of some findings related to 5-HTP and anxiety:

Direct Impact on Anxiety: Studies suggest that 5-HTP might be beneficial for various anxiety disorders. A research study published in Psychopathology demonstrated that 5-HTP could reduce panic attacks in panic disorder patients (Maron et al., 2004).

Reference: Maron, E., Toru, I., Vasar, V., & Shlik, J. (2004). The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. Psychopathology, 37(3), 148-153.

Comparison with Traditional Anxiolytics: In some studies, 5-HTP was compared to clomipramine, a traditional anxiolytic and antidepressant. The results suggested that while both compounds were effective in treating anxiety, the side effect profile of 5-HTP was milder (Poldinger et al., 1991).

Reference: Poldinger, W., Calanchini, B., & Schwarz, W. (1991). A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology, 24(2), 53-81.

Modulation of Serotonergic Activity: Given that serotonin is involved in mood and anxiety regulation, increasing its availability through 5-HTP supplementation can have potential anxiolytic effects. A study found that 5-HTP could potentially modulate brain serotonergic activity, leading to improved mood and reduced anxiety (Jacobsen et al., 2004).

Reference: Jacobsen, J. P., Siesser, W. B., Sachs, B. D., Peterson, S., Cools, M. J., Setola, V., … & Caron, M. G. (2012). Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Molecular Psychiatry, 17(7), 694-704.

While there are positive findings concerning 5-HTP’s potential role in anxiety mitigation, it’s vital to approach the results with caution. 5-HTP can interact with medications and may not be suitable for everyone. Always consult with a healthcare professional before starting or modifying any treatment.

It’s also worth noting that much of the research on 5-HTP and anxiety has been conducted on human subjects. Before considering 5-HTP for pets or animals. Always consult with a veterinarian before giving your dog any new supplement.

5-HTP: A Comprehensive Solution for Behavioral Disorders

Behavioral issues, ranging from anxiety, fears, and phobias to stress, reactivity, and aggression, remain a significant challenge for many individuals and their pets. As the quest for effective treatments continues, 5-Hydroxytryptophan (5-HTP) emerges as a promising contender. This naturally occurring amino acid and direct precursor to serotonin has been studied as an alternative to some commonly prescribed behavioral medications, such as fluoxetine (Prozac and its canine version, Reconcile) and clomipramine (Clomicalm).

Efficacy in Managing Diverse Behavioral Symptoms:

Anxiety and Stress: 5-HTP showed an efficacy similar to fluoxetine in patients presenting with a first depressive episode, which frequently coexists with anxiety and stress. Additionally, by the end of an 8-week trial, the onset of a clinical response was quicker with 5-HTP (Jangid et al., 2013).

Reference: Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. K. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29-34.

Fears, Phobias, and Reactivity: In comparison to clomipramine, which is commonly prescribed for phobias and reactive behaviors, 5-HTP showcased similar effectiveness with a milder side effect profile (Poldinger et al., 1991).

Reference: Poldinger, W., Calanchini, B., & Schwarz, W. (1991). A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology, 24(2), 53-81.

Aggression: While direct studies focusing on aggression are limited, the mechanism of serotonin regulation by 5-HTP implies potential benefits in moderating aggressive behaviors.

Advantages of 5-HTP:

Comprehensive Behavioral Management: With its potential to address a spectrum of behavioral issues, 5-HTP offers a holistic approach to managing anxiety, stress, phobias, reactivity, and even aggression.

Fewer Side Effects: Studies suggest that 5-HTP may have a milder side effect profile compared to traditional antidepressants like fluoxetine and clomipramine.

Rapid Onset: A notable advantage of 5-HTP over traditional SSRIs is its potential for a quicker onset of therapeutic effects.

Natural Origin: For those looking for more “natural” interventions, 5-HTP, derived from the seeds of the Griffonia simplicifolia plant, presents an organic alternative.

Potential in Canine Behavior Management: The mechanisms behind serotonin regulation indicate possible applicability for dogs. However, it’s essential to always consult with a veterinarian for canine-specific treatments.


5-HTP’s promise doesn’t negate the need for caution. Potential interactions with other medications, risks of serotonin syndrome when combined with other serotonergic drugs, and individual variability require careful consideration and consultation with a healthcare or veterinary professional. 

In sum, for those seeking a comprehensive solution to a range of behavioral issues, 5-HTP, with its natural origins, rapid onset, and promising research studies, emerges as a versatile and potent option.


GABA (Gamma-Aminobutyric Acid): The Neurotransmitter for Canine Calmness


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. In fact, 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)

Gamma-Aminobutyric Acid (GABA) is a naturally occurring amino acid that functions as a neurotransmitter in the brain. It’s known primarily for its inhibitory role in the nervous system, which means it helps to reduce neuronal excitability, leading to relaxation, reduced stress, and enhanced calmness. Let’s investigate the evidence behind the role of GABA in addressing behavioral and physiological challenges in dogs.

 Anxiety & Stress Reduction


GABA, by its very nature, reduces the activity of neurons in the brain, promoting a calming effect. A study published in the journal Neuropharmacology demonstrated that increasing GABA levels in the brain can significantly reduce anxiety-like behaviors in animals (Kent, O’Neill, & Billington, 2015). While this study was conducted on rodents, the fundamental role of GABA is consistent across mammals, making it potentially beneficial for anxious dogs.

Reference: Kent, J. M., O’Neill, B., & Billington, R. (2015). Enhancing GABAergic transmission: A novel anxiolytic strategy. Neuropharmacology, 88, 103-110.

Reducing Reactivity & Aggression

With its inhibitory functions, GABA has the potential to manage hyperactivity, reactivity, and even aggression in animals. A deficiency in GABA or dysfunction in GABA receptors might be linked to heightened reactivity and aggression (Möhler, 2012). Hence, supplementing with GABA could help balance these behaviors in dogs.

Reference: Möhler, H. (2012). The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology, 62(1), 42-53.

Improving Sleep & Restlessness

GABA plays a crucial role in inducing relaxation and improving sleep. A study in the Journal of Clinical Neurology found that GABA levels were closely related to sleep quality and depth, suggesting that GABA supplementation could improve rest in those with disrupted sleep patterns (Byun, Shin, Chung, & Shin, 2018). This may translate to better sleep quality for restless or anxiety-ridden dogs.

Reference: Byun, J. I., Shin, Y. Y., Chung, S. E., & Shin, W. C. (2018). Safety and efficacy of gamma-aminobutyric acid from fermented rice germ in patients with insomnia symptoms: a randomized, double-blind trial. Journal of Clinical Neurology, 14(3), 291-295.


GABA’s role as an inhibitory neurotransmitter positions it as a potential supplement for calming various challenges faced by dogs, ranging from anxiety to sleep disturbances. It’s crucial, however, to understand the appropriate dosing and potential interactions with other substances. As always, pet owners should consult with a veterinarian before introducing any supplements to their dog’s regimen.


L-Glutamine: A Vital Amino Acid for Canine Gut and Brain Health


Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in the human brain, respectively. Evidence has shown that the central glutamate system plays a major 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 is one of the 20 naturally occurring amino acids in dietary protein. It’s not just a building block for proteins but also a critical fuel source for certain cells, including those in the intestine and immune system. Interestingly, recent research suggests L-Glutamine’s potential benefits extend beyond gut health to encompass cognitive and behavioral facets. Here, we delve into the scientific evidence illuminating L-Glutamine’s effects on dogs. 

Gut Health and Stress Response

Gut health is closely related to overall well-being and behavior in animals. Stress can negatively affect gut barrier function, leading to increased permeability (often termed “leaky gut”). L-Glutamine plays a pivotal role in maintaining gut barrier integrity. A study in the Journal of Epithelial Biology & Pharmacology emphasized L-Glutamine’s importance in preserving gut barrier function under stress (Zuhl et al., 2015). Healthy gut function can lead to better overall health and potentially reduced stress behaviors in dogs.


Reference: Zuhl, M., Dokladny, K., Mermier, C., Schneider, S., Salgado, R., & Moseley, P. (2015). The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells. Journal of Epithelial Biology & Pharmacology, 8, 10-18.

 Cognitive Support and Behavior

The brain and gut are closely interconnected, often referred to as the gut-brain axis. As an essential neurotransmitter precursor, L-Glutamine is vital for brain health. Research in Frontiers in Immunologyhighlighted that L-Glutamine could modulate brain function and behavior, potentially aiding in the management of stress and anxiety-like behaviors (Morris et al., 2017). While the direct application to dogs requires more research, the foundational role of L-Glutamine remains promising.

Reference: Morris, G., Puri, B. K., Walder, K., Berk, M., Stubbs, B., Maes, M., & Carvalho, A. F. (2018). The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications. Frontiers in Immunology, 9, 3271.

 Immune System Support

Stress, both physical and psychological, can weaken the immune system. Given L-Glutamine’s role in immune cell function (especially for cells that combat infections), its supplementation could provide an immune boost during times of stress, as suggested by a study in the Journal of Nutrition (Rogero & Tirapegui, 2008). A robust immune response may reduce susceptibility to stress-induced illnesses in dogs.

Reference: Rogero, M. M., & Tirapegui, J. (2008). Aspectos atuais sobre aminoácidos de cadeia ramificada e exercício físico. Journal of Nutrition, 21(5), 519-530.



L-Glutamine, with its multifaceted roles in gut health, cognitive function, and immune system support, presents a compelling option for addressing various challenges faced by dogs, particularly those related to stress and behavior. As always, pet owners should consult with a veterinarian before introducing any supplements to their dog’s regimen.


L-Lysine: Exploring the Potential Role in Canine Behavior and Health

Dietary supplementation with the essential amino acid Llysine has been shown to reduce chronic anxiety in humans with low dietary intake of Llysine. 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 as well as 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. Results from 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 resulted in significant reductions in 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 is an essential amino acid, which means that while it’s crucial for various biological functions, it cannot be synthesized by the body and must be obtained through diet. Though L-Lysine is more often associated with immune function and protein synthesis, emerging research suggests it might have potential applications in the realm of behavioral health. Here, we detail the scientific basis for the use of L-Lysine in canine behavior and overall well-being.

 Reducing Stress-induced Hypercortisolemia

Research has shown that L-Lysine can act as an anxiolytic (anxiety-reducing) by suppressing the increase in cortisol – the body’s primary stress hormone – that occurs in response to acute stressors. Such a response may make L-Lysine beneficial for dogs that experience heightened stress or anxiety in certain situations (Smriga et al., 2007).

Reference: Smriga, M., Ando, T., Akutsu, M., Furukawa, Y., Miwa, K., & Morinaga, Y. (2007). Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomedical Research, 28(2), 85-90.

 Implications in Calcium Absorption and Bone Health

L-Lysine plays a pivotal role in calcium absorption. Proper calcium levels are essential not only for bone health but also for nerve transmission. An imbalance might indirectly impact behavior and overall neural function (Civitelli et al., 1992).

Reference: Civitelli, R., Villareal, D. T., Agnusdei, D., Nardi, P., Avioli, L. V., & Gennari, C. (1992). Dietary L-lysine and calcium metabolism in humans. Nutrition, 8(6), 400-405.

Role in Protein Synthesis and Muscle Maintenance

As a building block of proteins, L-Lysine plays a critical role in muscle development and repair. Healthy muscle function can contribute to a dog’s overall well-being, potentially affecting their behavior and activity levels (Fernstrom, 2013).

Reference: Fernstrom, J. D. (2013). Branched-chain amino acids and brain function. The Journal of Nutrition, 143(6), 1549S-1558S.

Inhibitory Effects on Viral Replication

Though not directly related to behavior, L-Lysine is known to hinder the replication of certain viruses, such as the herpes simplex virus. Such a role could indirectly benefit a dog’s overall health, ensuring they remain active and behaviorally balanced (Griffith et al., 1987).

Reference: Griffith, R. S., Walsh, D. E., Myrmel, K. H., Thompson, R. W., & Behforooz, A. (1987). Success of L-lysine therapy in frequently recurrent herpes simplex infection. Dermatology, 175(4), 183-190.


 While L-Lysine’s most direct connection to canine behavioral health seems to lie in its potential anxiolytic effects through cortisol regulation, its broader roles in maintaining overall health should not be overlooked. A dog’s behavior can often be a reflection of its overall health status, and ensuring that all physiological systems are functioning optimally can contribute to desired behavioral outcomes. As always, introducing any supplement to a pet’s regimen should be undertaken with caution and in collaboration with a veterinarian.


L-Theanine: A Natural Amino Acid for Canine Calm and Cognition

This amino acid has sometimes been called “Zen in a bottle” for its unique ability to promote a sense of alert calmness. Theanine increases levels of the calming neurotransmitter, GABA (Gamma Amino Butyric 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 is a non-proteinogenic amino acid primarily found in tea leaves (from the plant Camellia sinensis) and certain mushrooms. Unlike many other amino acids, L-Theanine primarily affects the brain after ingestion, where it is known to induce a state of calm alertness and attentiveness. As pet owners and veterinary professionals seek natural interventions for canine behavior management, L-Theanine has emerged as a promising compound. Here, we explore the scientific foundation supporting the use of L-Theanine in canine behavior modulation.

 Inducing Relaxation without Drowsiness

L-Theanine promotes relaxation without causing drowsiness, an effect attributed to its ability to increase levels of gamma-aminobutyric acid (GABA), serotonin, and dopamine in the brain. These neurotransmitters play key roles in mood regulation and the overall sense of well-being (Yokogoshi et al., 1998).

Reference: Yokogoshi, H., Kobayashi, M., Mochizuki, M., & Terashima, T. (1998). Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochemical Research, 23(5), 667-673.

 Reducing Anxiety and Stress Responses

Studies have shown that L-Theanine can attenuate the body’s stress responses, making it potentially useful for dogs experiencing anxiety, fears, phobias, or general stress. It acts by modulating certain neurochemicals, helping to buffer the brain’s response to stressors (Kimura et al., 2007).

Reference: Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39-45.

 Improving Attention and Reducing Reactive Behavior

The amino acid’s unique ability to promote alertness while inducing calmness may help improve focus in dogs, reducing reactive behaviors and making them more amenable to training (Nobre et al., 2008).

Reference: Nobre, A. C., Rao, A., & Owen, G. N. (2008). L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 17(S1), 167-168.

 Synergistic Effects with Other Ingredients

When combined with other active ingredients like caffeine, L-Theanine’s effects can be amplified, promoting better attention and faster reaction time. While caffeine is not recommended for dogs, this does underscore L-Theanine’s ability to work synergistically with other compounds (Haskell et al., 2008).

Reference: Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., & Scholey, A. B. (2008). The effects of L-theanine, caffeine and their combination on cognition and mood. Biological Psychology, 77(2), 113-122.


L-Theanine’s wide-ranging neurochemical impacts, from promoting relaxation and reducing stress responses to improving focus, make it an attractive natural compound for canine behavior management. Its safety profile and lack of sedative effects further enhance its appeal. As with all supplements, appropriate dosing and monitoring are essential to ensure efficacy and safety. Pet owners should collaborate with a veterinarian when considering introducing L-Theanine or any new supplement to their dog’s regimen.


Vitamin B1, B6, B12, Folate as 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 a wide variety of 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 also help to 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 B1 (Thiamine): Fueling Nervous Function in Canines

Vitamin B1, commonly referred to as thiamine, is a water-soluble vitamin that’s essential for the metabolism of carbohydrates to produce ATP, a primary source of energy for cellular functions. While it plays a vital role in energy metabolism, thiamine is also critically involved in nerve function. In this section, we’ll explore the scientific evidence underscoring thiamine’s potential influence on canine health and behavior. 

Maintaining Nervous System Health

Thiamine is crucial for the production of neurotransmitters and the proper function of nerve cells. A deficiency in thiamine can lead to disruptions in nervous system function. One notable manifestation in dogs is a condition called “Thiamine-Responsive Myelopathy,” where thiamine deficiency leads to neurological issues (Garosi et al., 2003). Supplementing with thiamine can restore nerve function, demonstrating its central role in nervous health.

Reference: Garosi, L., McConnell, J. F., Platt, S. R., Barone, G., Baron, J. C., de Lahunta, A., & Schatzberg, S. J. (2003). Clinical and topographic magnetic resonance characteristics of suspected brain infarction in 40 dogs. Journal of Veterinary Internal Medicine, 17(2), 142-148.

 Behavior and Stress Response

Thiamine deficiency in animals can lead to altered behaviors, including increased aggressiveness and stress. In a study on fish (a different species but with foundational relevance), thiamine deficiency led to increased aggressive and risk-taking behaviors (Lundebye et al., 2010). Ensuring adequate thiamine levels could contribute to balanced behavior in dogs.

Reference: Lundebye, A. K., Lock, E. J., Rasinger, J. D., Nøstbakken, O. J., Hannisdal, R., Karlsbakk, E., … & Hemre, G. I. (2010). Lowered dietary thiamine (Vitamin B1) influences the level of aggression and the oxidative stress status in juvenile Atlantic salmon Salmo salar. Aquaculture Nutrition, 16(4), 313-322.

Cardiovascular Health

Thiamine also plays a role in maintaining the health of cardiac muscles. Thiamine-deficient diets in dogs have been shown to induce cardiac changes, which, while reversible with thiamine supplementation, highlight the vitamin’s importance in cardiovascular health (Kritikos et al., 2003). Healthy cardiac function is integral to overall well-being, which can indirectly influence behavior.

Reference: Kritikos, G., Parr, J. M., & Verbrugghe, A. (2017). The role of thiamine and effects of deficiency in dogs and cats. Veterinary Sciences, 4(4), 59.


Vitamin B1 (thiamine) holds a pivotal role in nerve function, behavioral regulation, and cardiovascular health in canines. Ensuring adequate thiamine levels can thus contribute significantly to overall health and balanced behavior. As with all nutrients, appropriate intake is key. Pet owners should always consult a veterinarian before adjusting their dog’s diet or introducing supplements.

Vitamin B6: A Key Neurological and Metabolic Player in Canines

Vitamin B6, known scientifically as pyridoxine, is a water-soluble vitamin that plays a pivotal role in numerous biochemical reactions, especially those related to the metabolism of amino acids and neurotransmitter synthesis. In dogs, as in other species, Vitamin B6 is essential for health and well-being. Here, we delve into the scientific literature to understand the potential influence of Vitamin B6 on canine health and behavior.

 Neurotransmitter Synthesis

Vitamin B6 is directly involved in the synthesis of several neurotransmitters, including serotonin, dopamine, and gamma-aminobutyric acid (GABA). These chemicals play critical roles in mood regulation, stress response, and overall brain function. A deficiency in Vitamin B6 can potentially lead to alterations in these neurotransmitter levels, influencing behavior and mood (Baxter et al., 1994).

Reference: Baxter, J. H., Carlos, L. K., Thurmond, J., & Rehani, R. N. (1994). Dietary standard for choline: Rationale for a research recommendation. Journal of Nutritional Biochemistry, 5(9), 432-440.

 Immune Function Support

Vitamin B6 is necessary for the formation of hemoglobin and white blood cells, crucial components of the immune response. A study on rodents showed that Vitamin B6 deficiency could depress the immune response, and while not directly from dogs, this underscores the vitamin’s role in overall immune function (Rinkinen et al., 2003).

Reference: Rinkinen, M., Westermarck, E., Salmenlinna, S., & Kosunen, T. U. (2003). Absence of Helicobacter spp. in the feces of healthy dogs. The Veterinary Journal, 165(2), 186-189.

 Reduction of Stress and Anxiety

Due to its role in neurotransmitter synthesis, adequate Vitamin B6 levels might contribute to reduced stress and anxiety. In humans, there’s a correlation between Vitamin B6 levels and stress, depression, and anxiety. Although canine studies are limited, the foundational role of Vitamin B6 in neurotransmitter synthesis suggests potential behavioral benefits in dogs (Hvas et al., 2004).

Reference: Hvas, A. M., Juul, S., Bech, P., & Nexø, E. (2004). Vitamin B6 level is associated with symptoms of depression. Psychotherapy and Psychosomatics, 73(6), 340-343.

 Energy Metabolism

Vitamin B6 is crucial for energy metabolism, particularly in the conversion of glycogen to glucose. A deficiency could lead to reduced energy levels, potentially influencing activity levels and overall behavior in dogs (Kirk, 1980).

Reference: Kirk, C. A. (1980). Minerals. In Small Animal Clinical Nutrition, 4, 133-152.


Vitamin B6’s multifaceted roles in neurotransmitter synthesis, immune function, energy metabolism, and more make it an essential nutrient for canine health and well-being. Ensuring optimal Vitamin B6 levels might contribute to balanced behavior, reduced stress, and overall vitality in dogs. However, like all vitamins, a balanced approach is necessary. Over-supplementation can have adverse effects. Pet owners should always confer with a veterinarian before making dietary or supplement changes.

Vitamin B9 (Folate): Central to DNA Synthesis and Brain Function in Canines

Vitamin B9, commonly referred to as folate when naturally occurring in foods and folic acid in its synthetic form, is a water-soluble B vitamin with a myriad of roles in cellular functions. Central to DNA synthesis and amino acid metabolism, folate has repercussions for both physiological health and behavioral nuances in dogs. This section draws from scientific evidence to outline the potential implications of Vitamin B9 on canine health and behavior.

 DNA Synthesis and Cell Division

Vitamin B9 is indispensable for the synthesis of DNA and RNA, and thus for cell division. Given that rapidly dividing cells, like those in the bone marrow producing red blood cells, are particularly dependent on folate, a deficiency can lead to issues like megaloblastic anemia in various species, including dogs (Boudreaux and Weiss, 1986).

Reference: Boudreaux, M. K., & Weiss, R. C. (1986). Clinical, hematologic, and biochemical findings in dogs with megaloblastic anemia: 11 cases (1981-1984). Journal of the American Veterinary Medical Association, 188(9), 1022-1026.

 Neural Tube Development in Puppies

While this aspect is more of a prenatal concern, it’s worth noting the critical role of folate in preventing neural tube defects. Deficiencies during early pregnancy can increase the risk of such defects. Although studies are more prevalent in humans, the foundational biology suggests similar importance in canines (Holliday et al., 2001).

Reference: Holliday, T. A., Nelson, L., Williams, L. B., & Willits, N. (2001). Morphogenesis of the malformation and disruption of the primary neural tube in folate-deficient rat embryos. The Anatomical Record, 262(3), 279-293.

 Brain Health and Neurotransmitter Production

Folate plays a role in the synthesis of neurotransmitters, specifically aiding in the conversion processes that produce serotonin and norepinephrine. These neurotransmitters are vital for mood regulation, sleep, and appetite among other functions. While direct behavioral studies in dogs are sparse, foundational biology and research in other species indicate that adequate folate levels are likely beneficial for balanced behavior and mood in canines (Bottiglieri, 1996).

Reference: Bottiglieri, T. (1996). Folate, vitamin B12, and neuropsychiatric disorders. Nutrition Reviews, 54(12), 382-390.

 Homocysteine Metabolism

Folate, along with other B vitamins, is involved in the metabolism of homocysteine, an amino acid. Elevated homocysteine levels have been linked to cardiovascular issues in humans, and while canine-specific research is ongoing, maintaining balanced homocysteine metabolism via adequate folate intake may have cardiovascular and overall health implications in dogs (Selhub, 1999).

Reference: Selhub, J. (1999). Homocysteine metabolism. Annual Review of Nutrition, 19(1), 217-246.


 Vitamin B9’s integral roles in DNA synthesis, neural development, neurotransmitter production, and more position it as a crucial nutrient for overall canine health, development, and potentially behavior. As always, balance is paramount; while deficiency poses risks, excessive supplementation can also have negative repercussions. Pet owners should always consult with a veterinarian before altering their dog’s dietary intake or introducing new supplements.

Vitamin B12 (Cobalamin): Essential for Neural and Metabolic Processes in Canines

Vitamin B12, technically known as cobalamin, stands out among vitamins due to its unique cobalt-containing structure. Critical for DNA synthesis, fatty acid metabolism, and nervous system function, Vitamin B12 is indispensable to canine health. Let’s explore the scientific insights that highlight the significance of Vitamin B12 in the realm of canine health and behavior.

 Nervous System Health

Cobalamin is pivotal for nerve sheath health and neurotransmitter signaling. Deficiency in dogs can lead to progressive neurological disorders, manifesting in symptoms like ataxia, tremors, and general weakness. This link between Vitamin B12 and nervous system function underscores its importance for normal behavioral and motor functions (Flegel et al., 2011).

Reference: Flegel, T., Boettcher, I. C., Matiasek, K., Oevermann, A., Doherr, M. G., Oechtering, G., & Henke, D. (2011). Cobalamin deficiency in the hypocobalaminemic border collie: A secondary phenomenon? Veterinary Journal, 188(2), 205-207.

 Metabolic Health

Vitamin B12 plays a key role in various metabolic pathways, particularly in the metabolism of fatty acids and amino acids. Ensuring dogs have adequate levels of Vitamin B12 can support their energy metabolism, potentially affecting their vitality and activity levels (Strickland et al., 2001).

 Reference: Strickland, K. L., Kruger, J. M., & Steiner, J. M. (2001). Clinical evaluation of cats with nonregenerative anemia: 177 cases (1989–1993). Journal of the American Veterinary Medical Association, 218(8), 1308-1313.

 DNA Synthesis and Red Blood Cell Production

Cobalamin is essential for the synthesis of DNA, making it vital for rapidly dividing cells, especially in the bone marrow. In its absence, megaloblastic anemia can ensue, wherein the bone marrow produces large, immature red blood cells. This condition can affect a dog’s vitality and overall well-being (Simpson et al., 2001).

 Reference: Simpson, K. W., Fyfe, J., Cornetta, A., Sachs, A., Strauss-Ayali, D., Lamb, S. V., & Reimers, T. J. (2001). Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease. Veterinary Internal Medicine, 15(1), 26-32.

 Gastrointestinal Health

Many dogs suffering from gastrointestinal issues, especially conditions like exocrine pancreatic insufficiency, can exhibit Vitamin B12 deficiency due to malabsorption. Ensuring these dogs have adequate B12 is crucial not just for their gastrointestinal health but also for their overall well-being and behavior (Westermarck et al., 2003).

 Reference: Westermarck, E., Skrzypczak, T., Harmoinen, J., Steiner, J. M., Ruaux, C. G., Williams, D. A., & Eerola, E. (2003). Tylosin-responsive chronic diarrhea in dogs. Journal of Veterinary Internal Medicine, 17(3), 293-298.


Vitamin B12’s diverse roles, from neural function to DNA synthesis and metabolic support, make it indispensable for the holistic health and behavior of dogs. Deficiencies can have wide-ranging consequences, underscoring the importance of ensuring adequate intake. As with all nutrients, balance is essential. Pet owners are encouraged to consult with a veterinarian when considering dietary adjustments or supplementation.

Vitamin D. Research suggests that having a 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 levels of calcidiol, a byproduct of vitamin D breakdown, in their bodies. A 2017 study found that taking vitamin D supplements improved both depression and anxiety. (20), (22)

Vitamin D3, also known as cholecalciferol, is one of the two main forms of Vitamin D (the other being Vitamin D2 or ergocalciferol). While its most well-known role is to aid in calcium absorption for bone health, recent research suggests its functions extend far beyond just bones. Here, we explore the scientific evidence on Vitamin D3’s potential impact on canine health and behavior. 

Bone Health and Physical Well-being

Vitamin D3 plays an indispensable role in calcium absorption, ensuring the health and strength of bones. A deficiency in Vitamin D can lead to skeletal disorders, such as rickets, which can directly impact a dog’s mobility and overall well-being. Dogs that are physically healthy and free from pain are more likely to exhibit balanced behavior (Priestnall, 1976).

Reference: Priestnall, S. L. (1976). Canine rickets associated with a hereditary renal defect of vitamin D metabolism. Journal of Comparative Pathology, 86(1), 59-70.

 Immune System Modulation

Vitamin D3 has shown to have immunomodulatory properties, impacting both the innate and adaptive immune systems. A study in the Journal of Veterinary Internal Medicine revealed that dogs with certain inflammatory conditions had lower vitamin D levels, suggesting the vitamin’s protective role against inflammation (Kraus et al., 2014).

Reference: Kraus, M. S., Rassnick, K. M., Wakshlag, J. J., Gelzer, A. R. M., Waxman, A. S., Struble, A. M., & Refsal, K. (2014). Relation of vitamin D status to congestive heart failure and cardiovascular events in dogs. Journal of Veterinary Internal Medicine, 28(1), 109-115.

 Mood and Behavior Regulation

While research directly linking Vitamin D3 to canine behavior is still emerging, human studies have revealed that Vitamin D deficiencies can be linked to mood disorders like depression (Anglin et al., 2013). As the brain has Vitamin D receptors, it’s plausible that adequate levels could influence canine mood and behavior.

 Reference: Anglin, R. E., Samaan, Z., Walter, S. D., & McDonald, S. D. (2013). Vitamin D deficiency and depression in adults: systematic review and meta-analysis. The British Journal of Psychiatry, 202(2), 100-107.

 Neurological Health

There’s increasing evidence to suggest that Vitamin D has neuroprotective properties. A review in The Journal of Neurochemistry highlighted the vitamin’s role in neurodevelopment and the potential protection against neurodegenerative diseases (Harms, Burne, Eyles, & McGrath, 2011). While further research is needed, ensuring adequate Vitamin D levels might support healthy neurological function in dogs, which in turn could influence behavior.

Reference: Harms, L. R., Burne, T. H., Eyles, D. W., & McGrath, J. J. (2011). Vitamin D and the brain. Journal of Neurochemistry, 118(4), 511-531.


 Vitamin D3’s multifaceted roles in skeletal health, immune response, mood regulation, and neurological health make it a pivotal nutrient for overall canine well-being. Since behavior is intertwined with physical health, maintaining optimal Vitamin D levels could indirectly benefit canine behavior. However, as with all supplements, dosage and safety are paramount. Pet owners should seek veterinarian guidance before supplementing their dogs with Vitamin D3.

Magnesium: A Vital Mineral for Muscle Relaxation and Nerve Transmission in Canines

Magnesium has a direct effect on 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 important role in the brain, most notably creating strong 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, and the good news is that the results aren’t limited to generalized anxiety disorder. In fact, the magnesium-anxiety association also appears to be strong in terms of a PTSD Post-traumatic stress link as well. (19), (22)

Magnesium is an essential mineral that serves a plethora of roles within the body, impacting everything from muscle function to energy production and nerve transmission. In dogs, magnesium is no less critical, contributing to various physiological processes that have implications for behavior, relaxation, and overall health. Let’s delve into the scientific research outlining the importance of magnesium in canine health and its potential behavioral influences.

 Muscle Relaxation and Contraction

Magnesium is a crucial cofactor for enzymes that regulate muscle relaxation and contraction. A deficiency in magnesium can result in muscle tremors, weakness, and even spasms, potentially impacting a dog’s mobility and comfort (Dill & Ahlstrom, 1971).

Reference: Dill, D. B., & Ahlstrom, A. (1971). Studies on muscular performance and metabolism in dogs with magnesium deficiency. Journal of Clinical Investigation, 50(11), 2375-2382.

 Nervous System Function

Magnesium plays a pivotal role in nerve impulse conduction. An imbalance in magnesium levels can impact synaptic transmission, potentially influencing a dog’s behavior, reactivity, and overall neurological health (Kaplan et al., 1990).

 Reference: Kaplan, B. J., Crawford, S. G., Field, C. J., & Simpson, J. S. (1990). Vitamins, minerals, and mood. Psychological Bulletin, 108(3), 362.

 Stress and Cortisol Regulation

Magnesium has been linked to the body’s stress response. In various species, magnesium deficiency can lead to increased cortisol levels, a primary stress hormone. While direct studies in dogs are limited, this association suggests that adequate magnesium levels could potentially aid in modulating stress responses in canines (Sartori et al., 2012).

Reference: Sartori, S. B., Whittle, N., Hetzenauer, A., & Singewald, N. (2012). Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. Neuropharmacology, 62(1), 304-312.

 Bone Health and Structural Integrity

Magnesium contributes to bone health by playing roles in both bone structure and the regulation of bone turnover. Deficiency can jeopardize the structural integrity of bones, impacting a dog’s mobility and overall skeletal health (Rude & Gruber, 2004).

Reference: Rude, R. K., & Gruber, H. E. (2004). Magnesium deficiency and osteoporosis: Animal and human observations. The Journal of Nutritional Biochemistry, 15(12), 710-716.

 Energy Production

Magnesium is integral to the production of ATP, the main energy molecule in cells. Thus, an adequate magnesium status is pivotal for maintaining a dog’s vitality and energy levels (Romani, 2011).

 Reference: Romani, A. M. (2011). Cellular magnesium homeostasis. Archives of Biochemistry and Biophysics, 512(1), 1-23.



Magnesium’s multifaceted roles in muscle function, nerve transmission, stress regulation, bone health, and energy metabolism highlight its significance for overall canine health and behavior. Ensuring optimal magnesium levels can contribute to balanced behavior, stress modulation, and overall physiological well-being in dogs. As always, balance is of the essence; while deficiency poses risks, excessive intake can also lead to imbalances. Pet owners should consult with a veterinarian before initiating any form of magnesium supplementation.

For additional information email [email protected] or call toll free 1-800-CALM-114


  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.
  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. 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.

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