Evidence Update: Anxitane (L-theanine) for Anxiety in Dogs (and Cats)

In late 2014, I reviewed the evidence for Anxitane (l-theanine), an amino acid from the tea plant reported to have benefits for dogs with anxiety. At that time, my conclusion was:

The theoretical reasoning behind the potential value of l-theanine for treatment of anxiety in dogs is plausible, which means it could work. The research in humans shows some weak evidence for a possible benefit, but the evidence is not sufficient to allow firm conclusions. Likewise, the research evidence in dogs is limited and weak, and it is not possible to say with any confidence whether or not l-theanine has a meaningful benefit for dogs with anxiety. It could work, but at this point we don’t know if it actually does.

Since the product is likely safe, there is little risk in trying it in dogs with anxiety. However, without stronger evidence for a benefit, it should not be viewed as a substitute for therapies with better evidence of efficacy.

I was recently asked to see if there had been any new studies that might clarify the value of this product. In humans, there haven’t been any major changes. A more recent review of the human literature reported that “few short-term benefits were reported with l-theanine alone.” Some studies reported reduced tension and anxiety, but others did not confirm this and found negative effects on cognition as well as an increase in headaches. A variety of positive effects on attention, cognition, and memory were reported for the combination of l-theanine and caffeine, but this is not relevant to veterinary patients due to the risks of caffeine in dogs and cats, and this would not be relevant to the use of l-theanine for anxiety anyway.

Here are a few additional veterinary studies not included in my last review.

Kern L. La transmission de la peur. In: La communications. Collection Zoopsychiatrie. Beata C. ed. Marseille, Solal Editeurs, 2005:191-6. (translation provided by the manufacturer of Anxitane)

This is not a new study but one that has only been published in French in a book on animal behavior, not in a peer-reviewed journal. The manufacturer of Anxitane has made it available as part of the marketing efforts for the product.

This was not really a clinical trial so much as a “try-it-and-see” report. Essentially, owners gave the l-theanine for two months to dogs they felt had a wide variety of behaviors assumed to be related to fear. The veterinarians then evaluated the dogs’ behavior at intervals (at the beginning, at 15 days, 30 days, and 60 days after starting the Anxitane) and decided whether they had improved. Not surprisingly, given the lack of bias controls in this study, the assessment was that the behavior improved.

Dramard V. Kern L. Hofmans J. et al. Clinical efficacy of l-theanine tablets to reduce anxiety-related emotional disorders in cats: A pilot, open-label clinical trial. 6th IVBM Conference. 2007. Riccione, Italy.

This is not actually a new publication since 2014, just one I hadn’t seen previously. It was also another “try-it-and-see” report rather than a controlled clinical trial. 33 cats with a wide variety of symptoms assumed to be due to anxiety were given l-theanine and then the owners and vets subjectively rated whether these were improved. The caregiver placebo effect, and numerous other potential confounders and sources of error, make the results of this study pretty unreliable. Funding was not disclosed, but one of the authors is an employee of the manufacturer of Anxitane.

Pike AL. Horwitz DF. Lobprise H. An open-label prospective study of the use of l-theanine (Anxitane) in storm-sensitive client-owned dogs. J of Vet Behav. 2015;4(10):324-31.

In this study, owners of dogs with storm phobia were recruited online and from general veterinary practices. Owners rated their dogs’ symptoms before and after using the supplement for at least 4 weeks or 5 storm events. Improvements were noted on most, but not all, behaviors measured. However, as the authors themselves acknowledge, the lack of the standard clinical trial bias controls (randomization, blinding, and placebo control group) made the results highly susceptible to caregiver placebo effects. The study was funded by the manufacturer of Anxitane.

Michelazzi M. Berteselli GV. Talamonti Z. et al. Efficacy of L-Theanine on noise phobias in dogs: preliminary results. Veterinaria (Cremona). 2015;29(2):53-9.

This study randomly assigned 10 dogs with noise phobia to receive behavioral therapy and Anixtane or just behavioral therapy. Assessment was by owner questionnaire and both owners and investigators were unblinded. There was no placebo or positive control. The funding source was not disclosed. Most behaviors measured improved over time in both groups. Some appeared to improve more in the animals given Anxitane while others, and the overall score, did not differ between the groups. Due to the subjective assessment and lack of controls, this study is at high risk of bias.

Bottom Line
While the basic principle that l-theanine might have clinically useful effects based on its biochemistry is plausible, there is still little compelling evidence it actually helps patients in the real world. A handful of studies have been done in humans, and the systematic reviews that have assessed them do not find strong evidence of benefit for anxiety in people. There have also been a handful of veterinary studies. Most of these are uncontrolled, unblinded, and use relatively subjective measures of outcome, and most are funded by the manufacturer. All appear to show benefits, but all are at high risk of bias. No significant risks have yet been seen, though headaches and some negative effects on mental function have been reported in humans.

All of this leaves us right where we were four years ago. Could work, might work, not sure if it does work, probably doesn’t do much harm. The frustrating thing is that the first low-quality attempt to study l-theanine for anxiety in dogs was reported by the manufacturer 13 years ago. Since then, the company has funded a few more unblinded, uncontrolled studies, but no high-quality, properly controlled clinical trials.  The product has been on the market for 9 years, yet the company has not funded such a study, nor has any independent research been published that accounts for the limitations of the existing literature. This is an all-too-typical pattern I have previously illustrated this way:

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8 Responses to Evidence Update: Anxitane (L-theanine) for Anxiety in Dogs (and Cats)

  1. Robin Wenham says:

    Maybe helpful to insert “massive profit” in the graphic illustration of the life cycle?

  2. Jerold Sorbel says:

    Is there any drug that actually relieves anxiety in dogs and not just turn them into zombies?

  3. George Butel says:

    Because I have a parrot, I watch for studies dealing with substances that show promise as safe anxiolytics for birds. I have wondered about theanine for a long time, having seen it recommended by those on the “holistic” bandwagon a couple of decades ago, a recommendation based, apparently, on the work of two well-known scientists, They Say, and Everybody Knows. Two fairly recent works on theanine caught my attention.

    The first, on rats, a Chinese study last year, surprised me a little. The verbiage at the beginning of their paper suggests that Yan, et al, might not have been totally dispassionate about the effects of theanine to begin with, judging by their apparent uncritical acceptance of other work, but they did add to the biochemical basis for theanine’s activities. (Let me point out, though, that this was published in a Hindawi journal.)
    “L-theanine administration had decreased serum glucose probably by inhibiting intestinal SGLT3 and GLUT5 mRNA expression in rats. Dietary fatty acids uptake might be suppressed by downregulating GPR120 and FABP2 transcripts in the intestine of rats. Meanwhile, intestinal transporters responding to AAs absorption were upregulated by L-theanine administration. Our data provide theoretical basis for further investigation of L-theanine and nutrients interaction.” (https://www.hindawi.com/journals/bmri/2017/9747256/).

    The other paper, from a multi-national group, also provides some biochemical rationale for physiological effects of theanine, this time in broilers. This study seemed to be of decent quality, and also brings up an issue that’s bothered me for a long time–the possibility of adverse effects, in this case, from higher doses–might be of concern. I don’t recall seeing any of the advocates of its use on birds worry much about “inconsequential” matters such as what an actual reasonable dosage might be. Saeed, et al, found, “Supplementing broiler diet with L-theanine reduced (p = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines (IL-2 and INF-g) and reduced mRNA expression of TNF-a and IL-6 in thymus, and IFN-g and IL-2 in spleen in the treated group. Moreover, supplementation with 200 mg/kg of L-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level of L-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels of L-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens.”

    Neither of those had anything to do with measuring anxiolytic activity, but modulation of important physiological processes such as blood pressure cannot be ignored. Would it be conceivable that better BP and lipid levels might make a human—or another animal—feel better, and, thereby, less anxious?
    Theanine is metabolized in humans this way: “L-theanine is rapidly absorbed and seems to be hydrolyzed to ethylamine and glutamic acid. A minor part of L-theanine is retained in erythrocytes. Kinetics and urinary excretion of L-theanine, ethylamine, and glutamic acid are comparable after both treatments. Thus, functional effects of L-theanine intake may result from L-theanine, ethylamine, or glutamic acid.” (Scheid, et al, 2012: https://academic.oup.com/jn/article/142/12/2091/4630725)

    Even if the substance is an effective anxiolytic, it isn’t something that one should start adding teaspoons of to a dog’s food (or even to one’s own food.) Since green tea is well-known as a source of theanine, some pet owners might be tempted to administer green tea extract, without thinking about the caffeine that’s present in most extracts. Or, they might decide to use a supplement such as that from Solaray or Thompson, both of which are sold as L-theanine, but which also contain green tea leaf (not likely enough to worry about, though.)
    There is a fascinating review of its effects in an article in the Asian Pacific Journal of Tropical Biomedicine last year. Warning; take a grain of sodium chloride (or, better, potassium chloride) before reading it though. It appears almost as though Adhikary and Mandal are promoting its use to cure all diseases known to mankind.

    There is no law against being cautious. Based on that one finding in the case of poultry, I would be extremely careful with dosage if I were going to use it.

  4. Andria says:

    Great summary – thanks for this!:) Quick error to report in the paragraph above “Bottom line”. The first sentence reads “This study randomly assigned 10 dogs with noise phobia to receive behavioral therapy and anxiety…” – assuming it should be “…with Anxitane…”.

  5. skeptvet says:

    There are many medications which can be used for anxiety, and their effects are highly variable between dogs. Serious side effects are uncommon, but sedation does occur with some medications in some dogs, and which often it improves with continued use, it can limit the usefulness of some drugs in some patients. The best we can do at this point is combine behavior modification therapy with trials of medications based on the specific needs and reactions of each individual patient.

  6. Is L-theanine completely safe? I have a lil pup. So i was thinking will it be harmful for lil puppy?

  7. skeptvet says:

    Nothing is “completely safe,” but so far there haven’t been any reports of side effects in dogs, and the only adverse effects reported in people have been mild (e.g. headaches), so the risk is probably very low.

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