Medical Hypotheses 145 (2020) 110397

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Ractopamine residue in meat might protect people from Parkinson disease

Frank S. Fan 1
Section of Haematology and Oncology, Department of Medicine, Ministry of Health and Welfare Taitung Hospital, Taitung County, Taiwan

A R T I C L E I N F O A B S T R A C T

Keywords: There is still no curative treatment for the exasperating Parkinson disease, the second most common neurode­
Parkinson disease generative disorder. Intracytoplasmic Lewy body composing of phosphorylated α-synuclein in dopaminergic
β-Adrenoreceptor neuronal cells has been recognized as the characteristic pathologic change and believed to be the cause of
α-Synuclein
neuronal cell loss in Parkinson disease. Recently, β-adrenoreceptor antagonist was found to be correlated with an
Ractopamine
increasing incidence of Parkinson disease and β-adrenoreceptor agonist, capable of inhibiting gene expression of
α-synuclein, was associated with a reduced incidence of it. Therefore, a hypothesis is raised that ractopamine, a
β-adrenoreceptor agonist used as feed additive for increasing leanness of finishing cattle and swine, might
provide protective effects for Parkinson disease and lower its incidence in the population consuming meat
containing ractopamine residue.

Introduction acid levels, regular physical activity, use of non-steroid anti-inflamma­

Parkinson disease, the second most common neurodegenerative
disorder after Alzheimer disease, occurs in 0.3% of the general popu­
lation with 1% to 2% of the people over the age of 60 years affected [1].
Diagnosis of Parkinson disease depends on clinical presentation of motor
symptoms, such as tremor, rigidity, bradykinesia and postural insta­
bility, and non-motor symptoms including olfaction loss, sleep disorder,
constipation and depression. The main pathologic changes in the central
nervous system of Parkinson disease patients are degeneration of
dopaminergic pigmented neurons in the substantia nigra and intra­
cytoplasmic accumulation of misfolded protein Lewy bodies in the brain
stem [2]. Levodopa remains as the standard treatment for motor
symptoms of Parkinson disease with a late complication as dyskinesia.
The exact aetiology of Parkinson disease is unknown and there is still no
effective prevention strategy. Herein, a hypothesis is raised in hope that
promotion of meat containing ractopamine residue might provide help
in this regard.
Risk and protective factors for Parkinson disease
Traditionally, according to several longitudinal investigations, high
risk of Parkinson disease has been associated with exposure to pesti­
cides, contact with solvents, consumption of dairy products, history of
melanoma, and traumatic brain injury, while protective factors seem to
be smoking (nicotine), coffee or tea drinking (caffeine), high serum uric
tion drugs, statin, and dihydropyridine calcium channel blockers [3,4].
Generally, life styles are not easy to be changed except for increasing
physical activity in the prodromal phase of Parkinson disease. Never­
theless, recent studies disclosed a novel direction of neuroprotection
regarding β-adrenergic receptors.
α-Synuclein and β-adrenoreceptor
In Parkinson disease, the major component of the pathogenic intra­
neuronal Lewy body is phosphorylated α-synuclein. Overexpression of
α-synuclein by duplication or triplication of its gene SNCA have been
documented in familial Parkinson disease while overproduction of
α-synuclein by dysregulation of SNCA seems responsible for sporadic
Parkinson disease. Interestingly, β2-adrenoreceptor was found to be
closely linked to regulation of SNCA. β2-adrenoreceptor antagonists,
such as propranolol, were associated with increased risk of Parkinson
disease, whereas β2-adrenoreceptor agonists such as salbutamol, pro­
vided protective effects and reduced the risk of Parkinson disease as
shown in both laboratory research and epidemiology studies conducted
in Norway and Israel [5,6].
Hypothesis
Ractopamine is a well-known feed additive used by beef and pork
producers for increasing leanness and lowering the percentage of fat in

E-mail address: fantast.fan@msa.hinet.net.

1
ORCID iD: 0000-0002-8123-6941

https://doi.org/10.1016/j.mehy.2020.110397
Received 13 September 2020; Received in revised form 14 October 2020; Accepted 9 November 2020
Available online 14 November 2020
0306-9877/© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
F.S. Fan
the past two decades. It has been approved to use in the United states,
Canada and Brazil. Meat from these countries are exported to other
countries as a big business. Pharmacologically, ractopamine is classified
as a β-adrenoreceptor agonist, acting on both β1-adrenoreceptor and β2-
adrenoreceptor with similar affinities but probably coupling more effi­
ciently to adenyl cyclase through β2-adrenoreceptor [7]. Since most
mammalian cells have β-adrenoreceptor in the cell membrane, it seems
confident to hypothesize that consumption of meat containing ractop­
amine residue might reduce the incidence of Parkinson disease in a long-
term perspective. Notably, South Korea lifted the ban on beef imports
from the United States in 2008 and the incidence of Parkinson disease
had decreased significantly from 2012 to 2015 [8].
Discussion
Parkinson disease is estimated to be the fastest growing neurode­
generative disease in the world. Novel therapeutic modalities are thus
being intensively developed, aiming at slowing pathologic progress,
reducing neuronal loss rate, and attenuating the disease course by trying
to clear α-synuclein accumulation, restore mitochondria function,
reduce neuroinflammation, inhibit α-synuclein propagation, and even
adopt embryonic stem cell rescue [9]. Gene-targeted therapies, chiefly
focusing on genetically linked targets SNCA (α-synuclein), LRRK2
(leucine-rich repeat kinase-2), and GBA1 (glucocerebrosidase), have
also been approached ambitiously [10]. Nonetheless, most clinical trials
testing these ideas are still in very early stages and a few have failed. In
the near future, it seems that preventative policy such as β2-adrenor­
eceptor agonist might be more hopeful in lowering the incidence of
Parkinson disease. Surprisingly, consuming meat containing ractop­
amine may turn out to be a “nature” preventive strategy and warrant
long-term epidemiologic cohort studies.
On the other hand, recent progress in computational chemistry uti­
lizing quantum chemical and molecular mechanics has predicted that
ractopamine not only interacts with β-adrenoreceptor but also trace
amine–associated receptor 1 (TAAR1) [11,12], and the latter was
proved in a cell model study, in which ractopamine was disclosed to be
an agonist for TAAR1 [13]. Based on the fact that TAAR1 has a wide
distribution in the central nervous system [14], it could be speculated
that behaviour adverse effects of pigs on ractopamine-containing feed
might be related to activation of TAAR1. In addition to that, interaction
of ractopamine and TAAR1 was found to reduce firing frequency of
dopamine neurons of the ventral tegmental area [15]. These bring a
great challenge to the hypothesized protective effect of ractopamine on
Parkinson disease raised above. Therefore, what seem mandatory are
more carefully designed investigations on this topic in the future.
Funding
This article has no funding source.
Medical Hypotheses 145 (2020) 110397
Declaration of Competing Interest
The author declares that he has no known competing financial in­
terests or personal relationships that could have appeared to influence
the work reported in this paper.
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