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Br J Sports Med 2001;35:342–343
Phenylethylamine, a possible link to theantidepressant eVects of exercise? Abstract
patients who are insensitive to conventional Objectives—To determine in this pilot
study whether aerobic exercise aVects
In view of the links between exercise and phenylacetic acid concentration in the
depression, and phenylethylamine and depres- sion, the relation between exercise and phenyl- Methods—Twenty healthy men provided
ethylamine also deserves attention. Further- 24 hour urine samples on two consecutive
more, phenylethylamine is involved in the days for the determination of phenylacetic
modulation of noradrenergic and dopaminer- acid levels. Before and during day 1,
gic synapses.2 In its role as an inhibitor of subjects refrained from physical activity;
noradrenergic reuptake, phenylethylamine may on day 2 subjects ran on a treadmill at 70%
be implicated in physical exercise. Considering that there is a dynamic equilibrium between (MHRR) for 30 minutes.
central and peripheral phenylethylamine, be-cause of its high lipid solubility and easy Results—The 24 hour mean urinary con-
passage through the blood/brain barrier, exam- centration of phenylacetic acid was in-
ination of the relation between phenylethyl- creased by 77% after exercise.
amine (as measured by urinary phenylacetic Conclusion—As phenylacetic acid con-
acid levels) and exercise is further warranted.
centration in urine reflects phenylethyl-
To the best of our knowledge, this study is the amine level, which is known to have
first attempt to test the eVects of exercise on antidepressant eVects, phenylethylamine
may be linked to the therapeutic eVects of
physical exercise on depression.
(Br J Sports Med 2001;35:342–343)
Methods
Twenty healthy male volunteers (mean (SD)
Keywords: depression; exercise; phenylacetic acid; phe- age 22.1 (4.1) years) agreed to be tested by signing an informed consent form. Their mean(SD) body mass index was 23.5 (1.6), their The current consensus is that physical activity mean (SD) resting heart rate was 64 (7.8) has antidepressant eVects.1 Indeed, doctors beats/min, and every week they exercised for widely recommend exercise either as treatment 2.6 (1.4) hours aerobically and 1.4 (1.3) hours for mild depression or as complementary treat- anaerobically. The subjects refrained from ment to drug and/or psychotherapy in cases of exercise for 24 hours (day 0) before the experi- more severe depression.1 The mode of action of volunteers for a 24 hour control non-exercising period (day 1). On day 2, the participants ran amine that has been linked to the regulation of on a treadmill (Powerjog JX100) at 70% oftheir maximal hear rate reserve (MHRR) for 30 minutes in the laboratory. This exercise inten- Monoamine oxidase B selectively metabolises sity was selected because a recent literature phenylethylamine to phenylacetic acid. There is evidence to indicate that levels of phenyl- ethylamine and phenylacetic acid are very low completion of the exercise and before recovery, in the biological fluids of depressed patients.3 subjects were asked to indicate the perceived As phenylethylamine turnover is very fast and intensity of their workout on a three point phenylacetic acid levels in the biological fluids (light, moderate, hard) rating scale. After the are far higher than phenylethylamine levels, it Department of Life
laboratory session, the participants collected has been suggested that phenylacetic acid Sciences, Nottingham
their urine for a further 24 hours (day 2). Once Trent University,
excretion is a better measure than phenylethyl- collected, the urine was kept at 4°C until trans- Nottingham, UK
amine for examining the modulatory role of ported to the laboratory where it was frozen.
phenylethylamine. Studies on urinary excre- Phenylacetic acid levels in the samples were tion of phenylacetic acid have shown that about stable using this protocol. Urinary volumes 60% of unipolar and bipolar patients have were all in excess of 0.8 litres.5 As the total lower than normal levels.2 Administration of weight of phenylacetic acid in the 24 hour urine was measured (mg/24 hours), the subjects were L-phenylalanine, in conjunction with selegiline, free to consume water or other liquids ad libi- Trent University, CliftonLane, Nottingham a selective monoamine oxidase B inhibitor, has been reported to alleviate depression and to The concentrations of urinary phenylacetic chromatography method of Gusovsky et al.5.
Phenylacetic acid and exercise: link to depression? role in the commonly reported “runners high”thought to be linked to cerebral activity. The substantial increase in phenyl- acetic acid excretion in this study implies thatphenylethylamine levels are aVected by exer- relatively homogeneously, there was consider-able interindividual variability in the phenyl-acetic acid responses to exercise (fig 1).
Interestingly, 17 of the subjects rated theexercise level as moderate, whereas three (11, 18, and 19 in fig 1) rated it as hard. Two of thelatter (subjects 18 and 19) also showed the most noticeable increase in phenylacetic acid in the following 24 hours. (It should be noted that our statistical conclusions would not change if the outlier cases, 18 and 19, were disregarded.) The lack of significant correlation between pheny- Percentage diVerence in urinary phenylacetic acid after exercise. Phenylacetic lacetic acid levels before and after exercise indi- acid concentrations were measured as mg/24 hours and percentages are compared with cates that the former only accounted for about 11% (r = 0.33; r2 = 0.11) of the changes in the Each sample was run in the presence of a stand- latter. Consequently, many factors may mediate ard concentration of an internal control, phenyl- phenylacetic acid responses to exercise, possibly propionic acid. Standards of phenylacetic acid in including perceived and/or actual exercise the range 10–40 µg/ml were used to calibrate intensity. Determination of these factors re- the column. Peak areas of phenylacetic acid/ mains the object of future inquiries.
phenylpropionic acid were calculated and used incentive for further research into the mecha-nism(s) linking phenylethylamine to exercise.
Such research should consider some important In 18 of the 20 subjects, the level of phenyl- factors that were not addressed in this pilot acetic acid in the urine was higher after study. Firstly, the inclusion of a passive activity exercise, increasing by 14–572% compared control group is advised. Secondly, instead of with the values before exercising (fig 1). The relying on MHRR as here, future studies need mean (SD) value of phenylacetic acid before to assess the actual VO MAX of the participants.
Thirdly, the changes in phenylacetic acid may 176.0 (47.7) mg/24 hours after exercise. The be diVerent in a sedentary sample in contrast diVerence between the two measurements was with the relatively fit and physically active sam- ple tested here. Therefore the influence of (ES) = 1.2). The correlation between the two fitness on phenylacetic acid levels also needs to sets of scores, however, was not significant be examined. Finally, the eVects reported here should also be examined in a clinicallydepressed population.
Discussion
These results show substantial increases in uri-
1 Mutrie N. The relationship between physical activity and nary phenylacetic acid levels 24 hours after clinically defined depression. In: Biddle S, Fox K, BoutcherS, eds. Physical activity and psychological well-being. London: moderate to high intensity aerobic exercise. As phenylacetic acid reflects phenylethylamine 2 Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant eVects of PEA replacement. J Neuropsychiatry 1996;8:168–
levels3, and the latter has antidepressant eVects, the antidepressant eVects of exercise appear to 3 Sabelli H, Javaid J. Phenylethlyamine modulation of aVect: therapeutic and diagnostic implications. J Neuropsychiatry be linked to increased phenylethylamine con- Clin Neurosci 1995;7:6–14.
4 Ekkekakis P, Petruzzello S. Acute aerobic exercise and aVect: current status, problems and prospects regarding structural and pharmacological analogy be- dose-response. Sports Med 1999;28:337–74.
tween amphetamines and phenylethylamine, it 5 Gusovsky F, Sabelli H, Fawcett J, et al. Gas-liquid chroma- tographic determination of phenylacetic acid in urine. Anal is conceivable that phenylethylamine plays a Biochem 1984;136:202–7.
Take home message
A 30 minute bout of moderate to high intensity aerobic exercise increases phenylacetic acidlevels in healthy regularly exercising men. The findings may be linked to the antidepressanteVects of exercise.

Source: http://www.wisebrain.org/media/Papers/PheylethylamineAPossibleLink.pdf