Although Americans and Europeans share fairly similar cuisines, American pork recipes may contain an extra sprinkle of carcinogen. Ractopamine, a chemical commonly used in the American pork industry to produce leaner pigs more quickly, is thought to have the potential to cause cancer, cardiovascular diseases, and lower overall life expectancy (Zaitseva et al. 2014). For these reasons, it has been banned in many countries and regions around the world, including the major markets of China and the European Union (EU). In spite of this, it is legal in Brazil, Canada, and the US, being widely used in the latter (Vezzoni de Almeida V et al. 2012). As a possible carcinogen, ractopamine is thought to interrupt the system of checks and balances that cells maintain to regulate muscle growth. With the regulation system affected, the cells may grow continuously without stopping – unchecked, abnormal muscle mass regulation can result in tumors. Although many tumors remain stationary, tumors that become malignant, or start spreading around the body, can turn into life-threatening cancers that killed almost 600,000 people in the US in 2019 (CDC.gov).
While the complete effects of consuming ractopamine are still unknown as of 2021, a recent study suggests that ractopamine has the potential of being carcinogenic by interfering with muscle cells’ natural stress response and causing potential abnormalities in muscle mass regulation. Published in 2018, this study studies a potentially dangerous chemical widely used and consumed within the United States, a chemical that has the capability of affecting the health of ordinary Americans.
More precisely, the study was conducted by Dr. David Brown of Healx Limited and was sponsored by Zoetis, formerly known as Pfizer Animal Health. The study was published in 2018 in Scientific Reports. Dr. Brown and his group were attempting to find a significant correlation between ractopamine and an abnormality in muscle mass regulation; findings of abnormal regulation could be a sign of ractopamine’s carcinogenic properties.
The study expanded upon a slightly outdated study done to test the effects of another beta-adrenergic agonist – the chemical family of ractopamine – on the muscle cells of mice (Spurlock, D.M. et al. 2006). This study split mice into a control and experimental group, with each group being further subdivided into 2 subgroups by the length of exposure to the beta agonist. Once the mice were put down and analyzed, the researchers found that the beta agonist had the potential to promote muscle enlargement. Following a similar experiment procedure, Dr. Brown wanted to find changes in the skeletal muscle gene expression after exposure to ractopamine and further identify molecular processes that allow the chemical to modify muscle cells.
To conduct the experiment, female adult pigs weighing around 77lbs each were fed high-quality feed. The pigs were split into three distinct categories: A group with ractopamine added into the feed, a group vaccinated with the growth hormone reporcin, and a control group given food with no extra additions. Additionally, to strengthen and built upon the flaws of Spurlock’s low-subgroup counts, the groups of pigs were further subdivided into subgroups consisting of 10 pigs exposed to the drugs for 1, 3, 7, and 13 days and a subgroup of 15 pigs exposed to the drugs for 27 days, after which the pigs were euthanized and analyzed. Only three randomly selected pigs from each subgroup were used for further analysis.
Once the three pigs were chosen, the RNA from the pigs was extracted and purified, with the quantity of RNA measured and its RNA integrity number (RIN) taken. The RNA was then sequenced to be reverse transcribed into DNA. The genes of the samples were then analyzed and compared, and genes that expressed significant differences between the control and experimental groups were identified and further refined. Quantitative-PCR (qPCR) was performed on these genes. Proteins were then extracted and probed to form visualized bands using enhanced chemiluminescent (ECL) detection reagent. The data revealed themselves as blots, and the blotting data, in addition to the qPCR, were then analyzed to compare the three groups. This was done by finding changes in relative mRNA transcript abundances and using two-way analysis of variance to assess the data for the three groups, five time period subgroups, and the cross between the two. For significance to be accepted, the values of the variance had to be greater than 0.05.
The study revealed that ractopamine activated transcription factors, which control the rate of transcription of DNA. This means that the drug caused an increase in the amount of proteins coded in a cell, although not necessarily the amount of proteins formed. Ractopamine also increased skeletal muscle expression of some genes that were not identified, and increased the expression of mRNAs in others. The genes the drug activated are related to cellular stress, meaning ractopamine has a good chance of interrupting the cell’s stress responses. The results show that ractopamine has the potential to increase stress and disrupt the cell’s system of self-regulation. The expression of new genes could also mean that the cell’s broken stress response may be a result of muscle growth caused by ractopamine. The change in stress response has the potential of affecting muscle mass growth, which could result in tumors.
The study was conducted ethically and justly, with the methods doing as little harm to pigs as possible until the pigs were euthanized. While study was also built well, the sample size of pigs used for further analysis could have been increased from 3 pigs/subgroup, although this may have been due to resource limitations. The authors mentioned no flaws and did not admit to any further flaws. To improve the experiment in the future, the sample size of extracted pigs should be increased as much as possible, and extra subgroups at the time points of 60 and 90 days should also be added to increase the strength of the study and show the longer-term effects of the drugs.
Potential bias of the experiment could have come from many places. Although Pfizer was not involved with the collection or analyzation of data, Dr. Brown’s long history with the company could have biased the research towards company interests. Additionally, the study was supported by Zoetis (a pharmaceutical company) and the Biotechnology and Biological Sciences Research Council of the United Kingdom and the Republic of Ireland, who could have skewed the experiment towards their liking.
Regardless of the possible bias, the study demonstrates a potential link between ractopamine and its ability to disrupt and affect cellular processes. The next step of research should be finding out the role that the affected genes play in muscle mass regulation, which could further explain ractopamine’s link to cancer. Despite the possible carcinogenic effects, ractopamine will most likely continue to be legal in the US because it has not yet been proven to be harmful, although some change may occur once its effects are better known. However, people seeking to avoid ractopamine in the US should consider buying organic and/or locally raised pork and push for legislative change in the drug’s legality – with enough pressure, a ractopamine-free future in the US may arrive sooner than later.
Brown D, Ryan K, Daniel Z, Mareko M, Talbot R, Moreton J, Giles TCB, Emes R, Hodgman C, Parr T, et al. 2018. The Beta-adrenergic agonist, Ractopamine, increases skeletal muscle expression of Asparagine Synthetase as part of an integrated stress response gene program. Sci Rep. 8(1):15915. doi:0.1038/s41598-018-34315-9.
CDCBreastCancer. 2020 May 29. An Update on Cancer Deaths in the United States. Centers for Disease Control and Prevention. [accessed 2021 Feb 18]. https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm.
Spurlock, D. M., McDaneld, T. G. & McIntyre, L. M. 2006. Changes in skeletal muscle gene expression following clenbuterol administration. BMC Genomics 7, 320
Vezzoni de Almeida V, Costa-Nunes AJ, Miyada VS. 2012. Ractopamine as a metabolic modifier feed additive for finishing pigs: a review. Braz Arch Biol Technol 55:445–456.
Zaitseva NV, Shur PZ, Atiskova NG, Kiryanov DA, Kamaltdinov MR. 2014. Health risk assessment of exposure to ractopamine through consumption of meat products. Int J Adv Res 2:538–545
Featured Image Source
Unsplash.com, for free and fair reuse. https://unsplash.com/photos/URfQU3ibC1Y