🧘 Calming & Anxiety

🔭 Scientific Evidence

Adaptil is a synthetic version of the Dog Appeasing Pheromone (DAP) naturally released by lactating bitches to comfort their puppies. Unlike most calming supplements, Adaptil has been tested in over 23 peer-reviewed studies and clinical trials. The strongest study is a double-blind, placebo-controlled trial by Kim et al. (2010, Canadian Veterinary Journal) of 43 hospitalised dogs (24 DAP, 19 placebo), which found significant reductions in pacing (P=0.017), elimination accidents (P=0.038), and excessive licking (P=0.005) in the DAP group. A randomised, double-blind, placebo-controlled study of 24 Beagle dogs (Landsberg et al., 2015, PMC) found that DAP collars significantly reduced global fear and anxiety scores during thunderstorm simulation on both test days. A randomised controlled trial of 45 puppies (Denenberg & Landsberg, 2008, JAVMA) found DAP significantly reduced fear and anxiety in puppy classes and improved long-term socialisation over 12 months. A 2006 triple-blind placebo-controlled study (Mills et al.) found DAP reduced anxiety-related behaviour in problem dogs at veterinary clinics. However, a 2021 systematic review in Veterinary Evidence (Riddell et al.) rated the overall evidence base as weak to moderate, noting methodological variability across studies and that most benefits disappear when treatment stops. Adaptil is not a sedative and works best as part of a broader behaviour management programme.

📚 Research References

• Kim YM et al. (2010) — Efficacy of dog-appeasing pheromone (DAP) for ameliorating separation-related behavioral signs in hospitalised dogs. Double-blind, placebo-controlled, 43 dogs. Canadian Veterinary Journal / PMC
• Landsberg GM et al. (2015) — Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in Beagle dogs: a placebo-controlled study. 24 Beagles, randomised. PMC
• Denenberg S & Landsberg GM (2008) — Effects of dog-appeasing pheromones on anxiety and fear in puppies during training and long-term socialisation. Randomised controlled trial, 45 puppies. JAVMA 233(12)
• Mills DS et al. (2006) — A triple blind placebo-controlled investigation into the effect of DAP on anxiety-related behaviour in the veterinary clinic. Applied Animal Behaviour Science 98(1-2)
• Riddell A et al. (2021) — Can dog appeasing pheromone ameliorate stress behaviours associated with anxiety in mature domestic dogs? Systematic review. Veterinary Evidence journal (RCVS Knowledge)

🔭 Scientific Evidence

Zylkene contains alpha-casozepine, a bioactive peptide derived from bovine milk protein (casein) that binds to GABA-A receptors in a similar way to benzodiazepine drugs, producing a calming effect without sedation. The key canine clinical study is Beata et al. (2007), which recruited 38 dogs with anxiety disorders through certified veterinary behaviourists. Over 56 days, alpha-casozepine performed statistically equivalently to selegiline — a licensed veterinary anxiolytic medication — with no significant difference in anxiety reduction scores between the two treatments. Owner assessment was also statistically equivalent. Importantly, this study lacked a placebo group; for ethical reasons the comparison was made against a known active treatment rather than no treatment. A 2010 placebo-controlled dietary study (Palestrini et al.) found alpha-casozepine reduced urine cortisol-to-creatinine ratios in dogs exposed to a stressor, suggesting a measurable physiological calming effect. However, a systematic review of the available evidence (Veterinary Evidence, 2017) rated the overall quality as low to moderate, citing methodological weaknesses and confounding variables across the studies. A 2024 preliminary study at a veterinary clinic found a potential benefit for vet-visit anxiety but could not reach statistical significance due to small numbers. Zylkene has an excellent safety profile — no known sedation, no known side effects, suitable for puppies and pregnant dogs — and is widely recommended by vets as a first-line supplement before considering prescription options.

📚 Research References

• Beata C et al. (2007) — Effects of alpha-casozepine (Zylkene) versus selegiline on anxiety disorders in dogs. 38 dogs, 56-day trial. Journal of Veterinary Behavior: Clinical Applications and Research
• Palestrini C et al. (2010) — Placebo-controlled dietary study of alpha-casozepine in anxious dogs: reduced urine cortisol-to-creatinine ratio on vet visits. Journal of Veterinary Behavior
• Veterinary Evidence (2017) — Systematic review: Is alpha-casozepine efficacious at reducing anxiety in dogs? Rated evidence as low quality; direction of effect consistently positive but methodological weaknesses noted
• Nixon S et al. (2024) — Zylkene vs placebo for fear/anxiety during veterinary visits in dogs. Preliminary study, SSRN. Potential benefit observed but statistical significance not reached
• Miclo L et al. (2001) — Characterisation of alpha-casozepine, a tryptic peptide from alpha-s1 casein with benzodiazepine-like activity. FASEB Journal 15:1780-1782

🔭 Scientific Evidence

YuMOVE Calming Care contains four active ingredients: Lemon Balm (180mg), L-Theanine (150mg), Fish Protein Hydrolysate (45mg), and B Vitamins. No independent peer-reviewed clinical trial has been published specifically testing this product, so the science score is based on ingredient-level evidence. L-Theanine has the strongest canine evidence of the four ingredients. A 2010 randomised study of 20 dogs with noise phobia (Michelazzi et al.) found that dogs receiving L-Theanine alongside behavioural therapy showed a greater reduction in anxiety behaviours than those receiving behavioural therapy alone. A 2015 open-label study (Pike et al., ScienceDirect) of storm-sensitive dogs reported statistically significant reductions (P<0.0001) in global anxiety scores and specific behaviours including panting, pacing and drooling, with 94% owner satisfaction — however the study lacked placebo control and blinding, making results susceptible to caregiver placebo effect. Lemon Balm works on GABA pathways (the brain's natural calming system) and has some supporting human evidence for anxiety reduction, but limited canine-specific trials. Fish Protein Hydrolysate (alpha-casozepine derived from milk protein) has been shown in some studies to support calming signals in the brain. B Vitamins support nerve and brain function. The evidence base for this combination is promising but not yet backed by a high-quality double-blind, placebo-controlled canine clinical trial.

📚 Research References

• Michelazzi M, Berteselli GV, Talamonti Z et al. (2010) — Effectiveness of L-theanine and behavioural therapy in the treatment of noise phobias in dogs. 20 dogs, randomised. Veterinaria (Cremona)
• Pike AL, Horwitz DF, Lobprise H (2015) — An open-label prospective study of the use of L-theanine (Anxitane) in storm-sensitive client-owned dogs. ScienceDirect / Journal of Veterinary Behavior
• Araujo JA, De Rivera C et al. (2010) — ANXITANE tablets reduce fear of human beings in a laboratory model of anxiety-related behaviour. Journal of Veterinary Behavior, 5:268-275
• Dramard V, Kern L, Hofmans J et al. (2007) — Clinical efficacy of L-theanine tablets to reduce anxiety-related emotional disorders in cats: A pilot open-label clinical trial. 6th IVBM Conference
• Lintbells — YuMOVE Calming Care: triple-action formula targeting GABA, dopamine and serotonin pathways to support natural calming in dogs

🔭 Scientific Evidence

Zesty Paws Calming Treats contain nine active ingredients: Suntheanine (L-Theanine), Ashwagandha, Organic Chamomile, Hemp Seed Powder, Valerian Root, Organic Passionflower, L-Tryptophan, Organic Ginger Root, and Magnesium Citrate. No independent peer-reviewed clinical trial has been published specifically testing Zesty Paws Calming Treats as a complete product. The science score is based on ingredient-level evidence only. Suntheanine is a premium, standardised 99.95% pure form of L-Theanine — the same active ingredient studied in veterinary products like Anxitane — and carries the same moderate evidence base: a 2015 open-label study in storm-sensitive dogs showed significant anxiety reductions, though the study lacked a placebo control. Sensoril Ashwagandha has one published canine-specific placebo-controlled study that found a statistically significant reduction in urine cortisol-to-creatinine ratios (an objective stress marker) and fear and anxiety domain scores (P=0.03), published in the Journal of Veterinary Behavior. This is one of the better-controlled ingredient studies in any calming supplement. The remaining ingredients — Chamomile, Valerian Root, Passionflower, Hemp Seed, L-Tryptophan, Ginger, and Magnesium Citrate — have supporting evidence primarily from human studies or traditional use, with minimal canine-specific research. Zesty Paws is a NASC Quality Seal member and uses branded, standardised ingredient forms, which supports product consistency.

📚 Research References

• Pike AL, Horwitz DF, Lobprise H (2015) — Open-label study of L-theanine (Suntheanine/Anxitane) in storm-sensitive dogs. Statistically significant anxiety reductions. Journal of Veterinary Behavior (ScienceDirect)
• Araujo JA, De Rivera C et al. (2010) — ANXITANE (L-Theanine) tablets reduce fear of human beings in a laboratory model of anxiety-related behaviour in Beagle dogs. Journal of Veterinary Behavior 5:268-275
• Journal of Veterinary Behavior — Sensoril Ashwagandha canine placebo-controlled study: significant reduction in urine cortisol-to-creatinine ratio and fear/anxiety domain scores (P=0.03) in dogs
• Bestiepaws.com (2026) — Veterinary review of Zesty Paws Calming Bites: Suntheanine and Sensoril Ashwagandha rated as the most evidence-supported ingredients; remaining ingredients largely extrapolated from human studies