The production, metabolism, and inhibition of heterocyclic aromatic amines produced from cooking meat

By Nidhi Saha, BDSReviewed by Benedette Cuffari, M.Sc.Nov 25 2022

In a recent Food Science and Human Wellness study, researchers review the carcinogenic and mutagenic properties of heterocyclic aromatic amines (HAAs), which are common contaminants present in various food products. Additionally, the authors discuss natural mechanisms by which HAA production can be inhibited and the potential for flavonoids to mitigate the toxicity of these compounds.

Study: The role of flavonoids in mitigating food originated heterocyclic aromatic amines that concerns human wellness. Image Credit: Sea Wave / Shutterstock.com

What are HAAs?

Despite the numerous health benefits associated with the consumption of meat as a result of their high nutrient content, overheating and/or improperly cooking these food products can lead to the generation of toxic substances, including nitrosamines, polycyclic aromatic hydrocarbons, and HAAs.

HAAs, for example, contain at least one heterocyclic ring, as well as atoms of at least two different elements and at least one amine group. To date, over 30 different types of carcinogenic and mutagenic HAAs have been isolated and identified in overcooked meat products.

In addition to meat products, HAAs of varying concentrations and types have also been identified in other food products, including coffee and alcoholic beverages such as whisky, wine beer, brandy, and Japanese sake.

How are HAAs metabolized in the human body?

Following the consumption of food products that have been contaminated with HAAs, these chemicals enter the circulation and are subsequently absorbed and metabolized by the digestive system. Recent studies indicate that the gut microbiota may have a significant role in HAA conversion into genotoxic metabolites.

Intestinal bacteria, for example, likely activates HAAs by cleaving glucuronides-conjugated HAAs; however, further research is needed to confirm this hypothesis.

Conversely, glucuronidase activity by the intestinal microbiome may also be involved in the conversion of HAAs. In addition to glucuronidase, various other intestinal enzymes, such as sulfatase and nitro-reductase, may also contribute to the genotoxic potential of HAAs.

Monitoring HAAs

Methylimidaquinoline (MeIQx) and phenylimidazo(4,5-b)pyridine (PhIP), both of which are abundant HAAs, are commonly measured in urine samples to monitor the circulation of these chemicals in patients. 

Despite the ease of collecting urine for the detection and monitoring of HAAs, several challenges are associated with this approach, including the single selection of biomaterials and limited types of HAAs that can be detected through this type of biological sample. Thus, further work is needed to enable the identification of HAAs in other sample types for long-term monitoring purposes.

Factors that contribute to HAA formation

The process of heating meat, which contains the precursor molecules that are essential to produce HAAs, is also the ideal environment for this type of reaction. Notably, several factors involved in the cooking process can alter the type and amount of HAAs produced, such as the heating method, temperature, and total time.

HAA concentrations appear to rise as a high temperature heating process with a long duration increases. Conversely, long heating times in the presence of a humid environment resulted in reduced HAA production.

Milder heating approaches, such as steaming, boiling, and microwave heating, produce fewer HAAs. Comparatively, pan frying has been shown to produce more HAAs. 

In addition to heating time, altered levels of precursors present within meat products may also determine the amount of HAAs in the final cooked product. High levels of sugars, for example, which are important precursors for HAA formation, reduce the formation of HAAs, particularly when they exceed creatine levels. Certain sugars, such as those which are rich in both glucose and fructose, have also been shown to inhibit the production of HAAs.

How do flavonoids inhibit HAA?

There are four types of flavonoids, of which include flavonols, isoflavones, flavanols, and dihydroflavones. Certain flavonoids, including epigallocatechin gallate (EGCG), luteolin, and quercetin, have been shown to inhibit the synthesis of HAAs, including MeIQx, PhIP, and imidazoquinolinone (IQ). 

The likely mechanism by which flavonoids inhibit the formation of HAAs is through a free radical reaction wherein pyridine, pyrazine, and other free radicals are eliminated by the antioxidant activity of these substances.

This theory has been confirmed in one study demonstrating that naringenin, quercetin, and other flavonoids combine with phenylacetaldehyde to form specific compounds that bind to the active carbonyl group, thereby inhibiting further reactions between phenylacetaldehyde and creatinine to ultimately inhibit PhIP formation. Similarly, both apigenin and lutolin have been shown to exert antioxidant activities to reduce the formation of HAAs.

Conclusions

Further research will determine how flavonoid active sites and key functional groups prevent the development of HAAs. Selecting different types of flavonoids and studying their impact on HAA generation in real-life settings, such as a barbeque system, can provide a theoretical basis for managing the formation of HAAs and reducing their health risks.