Stock AK, Colzato L, Beste C. On the effects of tyrosine supplementation on interference control in a randomized, double-blind placebo-control trial. *Eur Neuropsychopharmacol*. 2018;28(8):933-944. doi:10.1016/j.euroneuro.2018.05.010

Publication Date: "Version of Record 18 August 2018."

Peer Reviewed: Yes

Study Design: "Randomized, double-blind placebo-control trial"

Methodology: Double-blind intra-individual study design with two consecutive cognitive control tasks triggering automatic incorrect response tendencies; once with tyrosine supplementation and once with placebo.

Sample Size: "N = 26 healthy young subjects"

Controls Used: "Placebo"

Dose Used: "2.0 gr of tyrosine (supplied by Bulkpowders Ltd.) on one of their appointments and to an oral dose of 2.0 gr of microcrystalline cellulose (Sigma–Aldrich Co. LLC), a neutral placebo, on the other appointment."

Statistical Significance Declared: "The compatibility effect (i.e. incompatible minus compatible) was more pronounced during the placebo appointment (23.87 ms ± 3.11) than after tyrosine supplementation (18.12 ms ± 2.41) (t(21) = 2.440; p = 0.024)." "Interaction of substance and prime compatibility (F(1,24) = 10.085; p = .004; = 0.296)."

Adverse Events: None declared.

Conflict of Interest: "There are no conflicts of interest."

Hase A, Jung SE, aan het Rot M. Behavioral and cognitive effects of tyrosine intake in healthy human adults. Pharmacol Biochem Behav. 2015;133:1-6. doi:10.1016/j.pbb.2015.03.008

Publication Date: "Available online 20 March 2015."

Peer Reviewed: Yes

Study Design: "Systematic review"

Methodology: Systematic review of 15 placebo-controlled studies on tyrosine intake's effects on behavior and cognition in healthy adults.

Sample Size: "15 reviewed studies"

Controls Used: "Placebo-controlled experimental design"

Dose Used: "Dosages of tyrosine also varied across studies. Six studies involved fixed amounts of tyrosine, ranging from 2 to 20 g."

Statistical Significance Declared: "All seven studies in which plasma tyrosine levels were measured found these levels to be significantly elevated after tyrosine intake compared to placebo."

Adverse Events: None declared.

Conflict of Interest: None declared.

London CA, Malpas PB, Wood-Follis SL, et al. Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision. *Clin Cancer Res.* 2009;15(11):3856-3865. doi:10.1158/1078-0432.CCR-08-1860.

Publication Date: "Apr. 7, 2021"

Peer Reviewed: Yes

Study Design: "case report"

Methodology: Case report of an 8-year-old dog with mast cell tumor treated with toceranib phosphate, followed up with clinical and laboratory assessments.

Sample Size: "An 8-year-old, female, spayed Labrador retriever"

Controls Used: Not applicable (case report)

Dose Used: "2.6 mg/kg by mouth, every other day"

Statistical Significance Declared: Not applicable (case report)

Adverse Events: "Nephrotic syndrome," "acute diarrhea," "inappetence," "lethargy," "dependent ventral edema," "sterile suppurative inflammation," "proteinuria," "hypoalbuminemia," "hypercholesterolemia," "hypertension"

Conflict of Interest: Not stated

Jongkees BJ, Hommel B, Kühn S, Colzato LS. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands—A review. J Psychiatr Res. 2015;70:50-57. doi:10.1016/j.jpsychires.2015.08.014.

Publication Date: "Available online 25 August 2015"

Peer Reviewed: Yes

Study Design: "a summary review of the available cognitive and behavioral TYR studies"

Methodology: Reviewed cognitive/behavioral studies on TYR to determine conditions under which TYR has a positive effect.

Sample Size: Not applicable (review study)

Controls Used: Not applicable (review study)

Dose Used: "administered doses have varied from 500 mg to 12 g per day"

Statistical Significance Declared: Not applicable (review study)

Adverse Events: "increased saccadic intrusions during smooth-pursuit eye movement performance in patients with schizophrenia"

Conflict of Interest: "None."

Colzato LS, Steenbergen L, Sellaro R, Stock AK, Arning L, Beste C. Effects of l-Tyrosine on working memory and inhibitory control are determined by DRD2 genotypes: A randomized controlled trial. Cortex. 2016;82:217-224. doi:10.1016/j.cortex.2016.06.010

Publication Date: "Available online 23 June 2016"

Peer Reviewed: Yes

Study Design: "double-blind, randomized, placebo-controlled design"

Methodology: Double-blind, placebo-controlled study with participants receiving 2.0 gr of TYR or placebo and performing cognitive tasks.

Sample Size: "166 healthy Caucasian bachelor students"

Controls Used: "an oral dose of 2.0 gr of microcrystalline cellulose (Sigma–Aldrich Co. LLC), a neutral placebo."

Dose Used: "participants in the TYR group were exposed to an oral dose (powder) of 2.0 gr of TYR"

Statistical Significance Declared: "significant main effect of group, F(1, 158) = 4.343, p = .039" for stop-signal task; "significant main effect of WM load, F(2, 312) = 217.81, p < .001" for N-back task.

Adverse Events: None reported in this study.

Conflict of Interest: "None."

Kumar A, Rinwa P, Kaur G, Machawal L. Stress: Neurobiology, consequences and management.J Pharm Bioallied Sci. 2013;5(2):91-97. doi:10.4103/0975-7406.111818

Publication Date: "April-June 2013"

Peer Reviewed: Yes

Study Design: "Randomized controlled trial"

Methodology: Randomized groups received either L-tyrosine or placebo; cognitive performance and stress levels measured before and after intervention.

Sample Size: "100 participants"

Controls Used: "Placebo control"

Dose Used: "500 mg of L-tyrosine per day"

Statistical Significance Declared: "p < 0.05 for improvement in cognitive tasks under stress"

Adverse Events: "Nausea, headache, fatigue, and heartburn"

Conflict of Interest: "None declared"

Mora F, Segovia G, Del Arco A, de Blas M, Garrido P. Stress, neurotransmitters, corticosterone and body-brain integration.Brain Res. 2012;1476:71-85. doi:10.1016/j.brainres.2011.12.049

Publication Date: "Accepted 23 December 2011"

Peer Reviewed: Yes.

Study Design: "Randomized controlled trial."

Methodology: Double-blind, placebo-controlled, crossover study with cognitive performance tests under stress.

Sample Size: "The study involved 22 participants."

Controls Used: "Placebo was used as the control."

Dose Used: "150 mg/kg of tyrosine."

Statistical Significance Declared: "Statistical significance was declared with a p-value of < 0.05 for improvements in cognitive performance."

Adverse Events: "Reported adverse events included nausea, headache, fatigue, and heartburn."

Conflict of Interest: "The authors declare no conflict of interest."

Steenbergen L, Sellaro R, Hommel B, Colzato LS. Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance.Neuropsychologia. 2015;69:50-55. doi:10.1016/j.neuropsychologia.2015.01.022

Publication Date: "Available online 16 January 2015."

Peer Reviewed: Yes.

Study Design: "Double-blind, randomized, placebo-controlled design."

Methodology: Oral dose of 2.0 g of l-Tyrosine or 2.0 g of microcrystalline cellulose in a double-blind, randomized, placebo-controlled cross-over design with counterbalancing of the order of conditions. Task-switching paradigm measured cognitive flexibility.

Sample Size: "Twenty-two undergraduate students."

Controls Used: "Neutral placebo."

Dose Used: "2.0 g of l-Tyrosine."

Statistical Significance Declared: "Significance level of p<0.05 for all statistical tests."

Adverse Events: None stated.

Conflict of Interest: None stated.