Br J Sports Med 2001; 35:342-343
© 2001 the British Journal of Sports
Medicine
Phenylethylamine, a possible link to the
antidepressant effects of exercise?
A
Szabo, E Billett and J
Turner
Department of Life Sciences, Nottingham Trent University,
Nottingham, UK
Correspondence to: Dr Billett, Department of Life Sciences,
Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK ellen.billett{at}ntu.ac.uk
Accepted for publication 21 May 2001 .
 |
Abstract |
Objectives—To
determine in this pilot study whether aerobic exercise affects
phenylacetic acid concentration in the urine.
Methods—Twenty healthy men provided 24 hour urine samples
on two consecutive days for the determination of phenylacetic
acid levels. Before and during day 1, subjects refrained from
physical activity; on day 2 subjects ran on a treadmill at 70%
of their maximal heart rate reserve (MHRR) for 30 minutes.
Results—The 24 hour mean urinary concentration of phenylacetic
acid was increased by 77% after exercise.
Conclusion—As phenylacetic acid concentration in urine
reflects phenylethylamine level, which is known to have
antidepressant effects, phenylethylamine may be linked to the therapeutic
effects of physical exercise on depression.
Key Words: depression; exercise; phenylacetic acid;
phenylethylamine
|
Introduction |
The
current consensus is that physical activity has antidepressant
effects.1
Indeed, doctors widely recommend exercise either as treatment for
mild depression or as complementary treatment to drug and/or
psychotherapy in cases of more severe depression.1
The mode of action of exercise, however, remains unclear.
Phenylethylamine is an endogenous neuroamine that
has been linked to the regulation of physical energy, mood, and
attention.2
Monoamine oxidase B selectively metabolises phenylethylamine to phenylacetic acid.
There is evidence to indicate that levels of phenylethylamine and phenylacetic acid are very
low in the biological fluids of depressed patients.3
As phenylethylamine turnover is very fast
and phenylacetic acid levels in the biological fluids are far higher
than phenylethylamine levels, it has been
suggested that phenylacetic acid excretion is a better measure
than phenylethylamine for examining the modulatory role
of phenylethylamine. Studies on urinary
excretion of phenylacetic acid have shown that about 60% of unipolar
and bipolar patients have lower than normal levels.2
Administration of phenylethylamine or its precursor L-phenylalanine, in conjunction with selegiline, a selective
monoamine oxidase B inhibitor, has been reported to alleviate
depression and to produce improvements in mood. The effects are
sustained and also apparent in some patients who are insensitive to
conventional treatment.2,
3
In view of the links between exercise and depression, and phenylethylamine and depression, the
relation between exercise and phenylethylamine also deserves
attention. Furthermore, phenylethylamine is involved in the
modulation of noradrenergic and dopaminergic synapses.2
In its role as an inhibitor of noradrenergic reuptake, phenylethylamine may be implicated in
physical exercise. Considering that there is a dynamic equilibrium
between central and peripheral phenylethylamine, because of its high
lipid solubility and easy passage through the blood/brain barrier,
examination of the relation between phenylethylamine (as measured by urinary
phenylacetic acid levels) and exercise is further warranted. To the
best of our knowledge, this study is the first attempt to test the
effects of exercise on phenylacetic acid levels.
|
Methods |
Twenty
healthy male volunteers (mean (SD) 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 mean (SD) resting heart rate was 64 (7.8)
beats/min, and every week they exercised for 2.6 (1.4) hours
aerobically and 1.4 (1.3) hours anaerobically. The subjects refrained
from exercise for 24 hours (day 0) before the experiment. Urine was
then collected by the volunteers for a 24 hour control non-exercising
period (day 1). On day 2, the participants ran on a treadmill
(Powerjog JX100) at 70% of their maximal hear rate reserve (MHRR) for
30 minutes in the laboratory. This exercise intensity was selected
because a recent literature review4
shows that changes in mood are commonly reported at 60–80% MHRR. On
completion of the exercise and before recovery, subjects were asked
to indicate the perceived intensity of their workout on a three point
(light, moderate, hard) rating scale. After the laboratory session,
the participants collected their urine for a further 24 hours (day
2). Once collected, the urine was kept at 4°C until transported to
the laboratory where it was frozen. Phenylacetic acid levels in the
samples were stable using this protocol. Urinary volumes were all
in excess of 0.8 litres.5
As the total weight of phenylacetic acid in the 24 hour urine was
measured (mg/24 hours), the subjects were free to consume water or
other liquids ad libitum.
The concentrations of urinary phenylacetic acid were determined by
the gas liquid chromatography method of Gusovsky et al.5.
Each sample was run in the presence of a standard concentration
of an internal control, phenylpropionic acid. Standards of
phenylacetic acid in the range 10–40 µg/ml were used to
calibrate the column. Peak areas of phenylacetic
acid/phenylpropionic acid were calculated and used in the
analyses.
|
Results |
In 18 of
the 20 subjects, the level of phenylacetic acid in the urine was
higher after exercise, increasing by 14–572% compared with the values
before exercising (fig 1
). The mean (SD) value of phenylacetic acid before
exercise was 99.4 (54.4) mg/24 hours and 176.0 (47.7) mg/24 hours
after exercise. The difference between the two measurements was
significant (F1,19 = 26.6, p<0.0001; effect size
(ES) = 1.2). The correlation between the two sets of scores, however,
was not significant (r = 0.33, p = 0.09).
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Figure 1 Percentage difference
in urinary phenylacetic acid after exercise. Phenylacetic acid
concentrations were measured as mg/24 hours and percentages are
compared with values obtained before exercise.
| |
|
Discussion |
These
results show substantial increases in urinary phenylacetic acid
levels 24 hours after moderate to high intensity aerobic exercise. As
phenylacetic acid reflects phenylethylamine levels3,
and the latter has antidepressant effects, the antidepressant
effects of exercise appear to be linked to increased phenylethylamine concentrations.
Furthermore, considering the structural and pharmacological analogy
between amphetamines and phenylethylamine, it is conceivable
that phenylethylamine plays a role in the
commonly reported "runners high" thought to be linked to cerebral
ß-endorphin activity. The substantial increase in phenylacetic
acid excretion in this study implies that phenylethylamine levels are affected by
exercise.
Although about 75% of subjects responded relatively homogeneously,
there was considerable interindividual variability in the
phenylacetic acid responses to exercise (fig 1
). Interestingly, 17 of the subjects rated the exercise
level as moderate, whereas three (11, 18, and 19 in fig 1) rated it as hard. Two of the latter (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
phenylacetic acid levels before and after exercise indicates that the
former only accounted for about 11% (r = 0.33;
r2 = 0.11) of the changes in the latter. Consequently,
many factors may mediate phenylacetic acid responses to exercise,
possibly including perceived and/or actual exercise intensity.
Determination of these factors remains the object of future
inquiries.
The present findings should serve as an incentive for further
research into the mechanism(s) linking phenylethylamine to exercise. Such
research should consider some important factors that were not
addressed in this pilot study. Firstly, the inclusion of a passive
activity control group is advised. Secondly, instead of relying on
MHRR as here, future studies need to assess the actual VO2MAX of the participants.
Thirdly, the changes in phenylacetic acid may be different in a
sedentary sample in contrast with the relatively fit and physically
active sample tested here. Therefore the influence of fitness on
phenylacetic acid levels also needs to be examined. Finally, the
effects reported here should also be examined in a clinically
depressed population.
|
References |
- Mutrie N. The relationship between physical activity and
clinically defined depression. In: Biddle S, Fox K, Boutcher S, eds.
Physical activity and psychological well-being. London: Routledge,
2000:46–62.
- Sabelli H, Fink P, Fawcett J, et al. Sustained
antidepressant effects of PEA replacement. J Neuropsychiatry
1996;8:168–71.[Abstract]
- Sabelli H, Javaid J. Phenylethlyamine modulation of affect:
therapeutic and diagnostic implications. J Neuropsychiatry Clin
Neurosci 1995;7:6–14.[Abstract]
- Ekkekakis P, Petruzzello S. Acute aerobic exercise and affect:
current status, problems and prospects regarding dose-response. Sports
Med 1999;28:337–74.[Medline]
- Gusovsky F, Sabelli H, Fawcett J, et al. Gas-liquid
chromatographic determination of phenylacetic acid in urine. Anal
Biochem 1984;136:202–7.[Medline]
| Take home message
A 30 minute bout of moderate to high intensity aerobic exercise
increases phenylacetic acid levels in healthy regularly exercising men.
The findings may be linked to the antidepressant effects of exercise.
|
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[Abstract]
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© 2001 BMJ Publishing Group Ltd & British Association of Sport and Exercise
Medicine
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Abstract
Introduction
