Want to keep learning?

This content is taken from the Queen's University Belfast's online course, Tackling Global Food Safety. Join the course to learn more.

Skip to 0 minutes and 1 second What are heterocyclic amines? Heterocyclic amines, or HCAs, are a group of chemical compounds that are produced when protein containing muscles foods - such as lamb, fish, beef, chicken, and pork are cooked at high temperatures. Cooking methods that produce HCAs include grilling, pan frying, baking, barbecuing, and deep frying. The higher the temperature and the longer the food is cooked, the more HCAs are formed. Boiling however, does not usually produce HCAs and there are no HCAs found in raw food. HCAs were discovered in Japan in 1977 when charred meat was shown to be mutagenic using mutagenicity assays. To date, more than 25 types of HCAs have been identified with different types of HCAs forming at lower or higher temperatures.

Skip to 1 minute and 2 seconds All HCAs have one aromatic and one heterocyclic structure. However, HCAs can be roughly classified into two groups - imidazoquinoline derivatives, also known as IQ-type compounds, and beta carbolines, known as non IQ-type compounds. Imidazoquinoline derivatives, or IQ-type compounds, are chemicals within the same group with similar chemical structures but a slight difference in functional groups. The formation temperature is between 100 and 300 degrees Celsius. Types of imidazoquinoline derivatives include IQ, IQx, MeIQ, MeIQx, DiMeIQx, TriMeIQx, 4-IQx, 8-IQx, 4-methylene-8-MeIQx, 7-MeIQx, DMIP, 1,5,6-TMIP, and iso-IQ. Beta carbolines, or non IQ-type compounds, are HCAs that form at over 300 degrees Celsius.

Skip to 2 minutes and 23 seconds Types of beta carbolines include A-alpha-C, methyl-A-alpha-C, Harman, Norharman, PhIP, Trp-P 1, Trp-P 2, Glu-P 1 and Glu-P 2, Orn P-1, Cre-P 1, and Lys-P 1. Amongst HCAs, there is also variability in the carcinogenic potency as defined by the International Agency for Research on Cancer, with some being classified as probable human carcinogens - such as IQ - while others are possible human carcinogens - such as MeIQ, MeIQx, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, Glu-P 1, and Glu-P 2. The three types of HCAs that are most abundant in the human diet are DiMeIQx, formed at low temperatures; MeIQx, formed at low temperatures; and PhIP, formed at high temperatures. All three types are possible human carcinogens, the IARC Class 2B.

Skip to 3 minutes and 43 seconds PhIP constitutes 3/4 of human HCA intakes. How are HCAs formed? In general, the precursors of heterocyclic amines are consisted of free amino acids, glucose, and creatinine or creatine. Creatinine is a component of skeletal muscles. HCAs are only formed from foods that come from muscle. The formation of HCAs is a two step reaction. An amino acid and glucose bind. This is known as the Maillard reaction. That compound then binds to creatine to form a HCA. The second step requires heat to occur, so this is how cooking temperatures impact formation. Let’s look at the suggested pathway for a formation of IQ-type compounds.

Skip to 4 minutes and 39 seconds When meat is cooked under high temperature, amino acids and sugar react together to form pyridine or pyrizine through the Maillard reaction. These compounds will undergo further transformation with participation of Strecker aldehydes and creatinine to produce imidazoquinoxalines.

Skip to 5 minutes and 2 seconds In the case of the non IQ-type compounds, the formation takes place through pyrolytic reaction among amino acids and proteins. Pyrolysis occurs at temperatures higher than 300 degrees Celsius and produces many reactive fragments through radical reactions. In terms of the risk to human health, HCAs are mutagenic and are therefore suspected carcinogenic compounds. They have been reported to increase the risk factor for human cancers in different target organs such as colorectal, stomach, lung, pancreas, mammary, and prostate cancers. However in their native state, HCAs are not carcinogenic. They become carcinogenic by bioactivation in the body through DNA binding to form DNA adducts. Therefore HCAs become carcinogenic through the way they’re metabolised.

What are Heterocyclic Amines?

HCAs are unique amongst contaminants because they are not found in foods before cooking.

The levels of “contamination” are dependent upon the cooking method used, how long cooking progresses and if other ingredients are included either pre-cooking or during cooking (such as marinades).

Unfortunately, we do not know the level of consumption of HCAs that corresponds with a significant increase in risk of cancer. For researchers studying these compounds, trying to accurately measure levels in food and defining how people cook their meat, provides the greatest challenges in accurately defining exposure in different populations.

This section summarises the different groups of HCAs, how they are formed and which ones have been shown to induce the greatest carcinogenic potential.

Share this video:

This video is from the free online course:

Tackling Global Food Safety

Queen's University Belfast