Research review: Does fish flavoring contribute to hyperthyroidism in cats?

A study conducted by Japanese researchers hypothesized that fish flavoring in pet food might contribute to feline hyperthyroidism, because of cats' lower ability to metabolize the chemical compounds found in the food.

“Organohalogen compounds such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widely used in industry. Because of their persistence and high bioaccumulative potency, PCBs and PBDEs have been detected in both animal species and humans at significant levels. These halogenated contaminants adversely affect the endocrine system and neurodevelopment. Moreover, hydroxylated metabolites of PCBs (OH-PCBs) and PBDEs (OH-PBDEs) disrupt thyroid hormone (TH) homeostasis and have been implicated in the pathogenesis of feline hyperthyroidism,” the researchers postulate.

The nitty gritty (what they did and how they did it)

PBDE has been suspected of causing hyperthyroidism in cats as it is found in higher levels in cats with this endocrine disorder. The source has been postulated to be house dust related to grooming behavior and food. With the increasing number of diagnoses of hyperthyroidism, it has been hypothesized that the causes are related to exposure to substances that affect thyroid hormone homeostasis. In addition, PBDE and related compounds have been demonstrated to be higher in cats than dogs in the same geographic region. The method for metabolizing and excreting these substances is theorized to be much less efficient in cats than dogs as well.

In a study published in December of 2015, Japanese investigators sought to determine the method of exposure to these substances and the way in which dogs and cats metabolized them. Blood samples were collected from 17 dogs and 11 cats presented to two Japanese veterinary hospitals for a variety of clinical treatments unrelated to hyperthyroidism. The owners filled out a questionnaire about lifestyle and diet. Livers from 10 healthy dogs and three cats euthanized for incurable and painful disease were harvested. Commercial canned and dry pet foods of the most popular types in Japan were obtained for comparison to dog and cat blood levels of PBDE and related compounds.

The compounds hypothesized to contribute to hyperthyroidism were found in far less volume in dog blood than in cat blood, suggesting that cats' ability to metabolize and eliminate these chemicals is less robust. However, it was also shown that much higher levels of a family of related substances was found in cat food than in dog food, suggesting a much higher level of exposure. In addition, dry cat food had far higher levels, implying a concentrating action during the processing of raw materials. Cats had a different metabolite profile in their blood than dogs did, suggesting a different pathway for transformation.

In the wet cat food, the types and volume of chemicals and their metabolites found were consistent with those found in fish used as raw material. Tests using liver samples indicate that cats consuming cat food containing this fish are exposed to higher levels of these toxic compounds, retain them for longer periods of time, and metabolize them less efficiently than dogs.

What our experts think

The feline specialist: Dr. Elizabeth Colleran, DABVP (feline practice), who contributed the summary above, notes that while this study is interesting, more research is needed to determine a definitive link.

“The limitations of this study are the in vitro nature of the investigation into metabolism using liver samples harvested from cats and dogs. The small number of cats and dogs included in the study is also worth noting,” she says. “Finally, and perhaps more importantly, the specific components of raw materials used in the food were not described.

“This is an intriguing study and one, that implies a relationship between fish ingredients and the rapidly increasing diagnosis of feline hyperthyroidism. Furthermore, the compounds studied have been shown to be neurotoxic and to affect calcium homeostasis. Whether this family of chemicals and metabolites is directly implicated in thyroid disease in the cat remains to be seen,” she says.

The endocrinologist: Dr. David S. Bruyette, DACVIM, says that, “the present study suggests that pet cats are exposed to methoxylated PBDEs (MeO-PBDEs) through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the cytochrome P450 dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.

“These results suggest that pet cats routinely ingest natural MeO-PBDEs in cat food products containing fish and retain their demethylated metabolites, OH-PBDEs, in the blood for a prolonged time. Further studies are needed to clarify the toxic effects of OH-PBDEs such as 6OH-BDE47 on thyroid homeostasis and to establish the relationship between the exposure level and occurrence frequency of feline hyperthyroidism in pet cats,” he says.

Mizukawa H, Nomiyama K, Nakatsu S, et al. Organohalogen compounds in pet dog and cat: Do pets biotransform natural brominated products in food to harmful hydroxlated substances? Environ Sci Technol 2016;50:444-452.