Heterocyclic amines: What Are They?

by Joost Nusselder | Last Updated:  June 5, 2022

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Heterocyclic amines are a group of chemicals found in meat that can cause cancer. They are formed when meat is cooked at high temperatures or charred.  They can also be found in smoked fish, as well as some processed foods and drinks. 

In this article, I’ll explain what heterocyclic amines are and how you can reduce your exposure to them.

What are Heterocyclic amines

The Scoop on Meat Carcinogens

What are HCAs?

HCAs are a group of nasty compounds that form when you cook meat at high temperatures. They’re like the bad guys in a movie, and they’re responsible for a lot of the health risks associated with eating cooked meat. Here’s the deal:

  • HCAs are formed when creatine or creatinine, amino acids, and sugar are cooked together at high temperatures.
  • The higher the temperature and the longer the cooking time, the more HCAs are formed.
  • Different types of meat and cooking methods can affect the amount of HCAs that form.
  • The most common HCAs are 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP) and 2-amino-3,8-dimethylimidazo (4,5-f) quinoxaline (MeIQx).

What are the Health Risks?

HCAs have been linked to an increased risk of cancer in humans. In animal studies, they’ve been linked to tumors in the mammary glands, lungs, colon, forestomach, and prostate. Plus, they’ve been detected in human tissues and organs, including the breast, colorectum, and prostate. Yikes!

What Can We Do?

The good news is that there are some steps we can take to reduce our exposure to HCAs. Here are a few tips:

  • Cook meat at lower temperatures and for shorter periods of time.
  • Choose leaner cuts of meat and trim off any visible fat before cooking.
  • Avoid charring or burning the meat.
  • Marinate your meat before cooking to reduce the formation of HCAs.
  • Eat more plant-based proteins like beans, nuts, and tofu.

The Chemistry of Five-Membered Heterocyclic Amines

What Are Five-Membered Heterocyclic Amines?

Five-membered heterocyclic amines are molecules made up of a ring of five atoms, usually one nitrogen and four carbon atoms. These molecules form the basis of many compounds, including nicotine and pyrrole.

Nicotine

Nicotine is an alkaloid, a naturally occurring organic compound with nitrogen in it. It’s made up of a pyrrolidine ring attached to a ring of pyridine, another heterocyclic amine.

Pyrrole

Pyrrole is an unsaturated five-membered heterocyclic ring containing a nitrogen atom. It’s usually found in a ring structure called a porphyrin, which is made up of four pyrrole rings.

Uses of Five-Membered Heterocyclic Amines

Five-membered heterocyclic amines have many uses, including:

  • Hemoglobin, myoglobin, and cytochromes all contain porphyrin rings in their centers, with an iron ion bound to oxygen.
  • Vitamin B12 is also made up of porphyrin rings.
  • Chlorophyll also contains porphyrin rings.

What Are Six-Membered Heterocyclic Amines?

What is Pyridine?

Pyridine is like benzene, but with a nitrogen atom taking the place of one of the carbon atoms. It’s used to give food a bit of a flavor boost. Pyridine is also part of two B vitamins: niacin and pyridoxine.

  • Niacin, also known as nicotinic acid, is found in most living things. It’s turned into a coenzyme called NAD, which helps with oxidation and reduction in cells. Not getting enough niacin can cause pellagra.
  • Pyridoxine, or vitamin B6, is involved in the metabolism of amino acids.

What is Pyrimidine?

Pyrimidine is a six-membered ring with two nitrogen atoms. It’s part of thiamine, also known as vitamin B1. Not getting enough thiamine can cause beriberi. Pyrimidine is also part of the nucleobases cytosine, uracil, and thymine. The other two nucleobases, adenine and guanine, are purines, which are made of a pyrimidine and imidazole.

So, if you’re ever feeling a bit under the weather, you might want to check if you’re getting enough of these six-membered heterocyclic amines!

Cooking Meat: What You Need to Know About Heterocyclic Amines

What are Heterocyclic Amines?

Heterocyclic amines (HCAs) are cancer-causing chemicals that form when you cook muscle meats like beef, lamb, pork, fish and poultry at high temperatures. So if you’re a fan of charring your steak or frying your chicken, you should know that you’re also cooking up some potentially dangerous chemicals.

What are the Risks?

Studies have linked high intakes of well-done, fried, or barbecued meats to an increased risk of stomach, colorectal, pancreatic, and breast cancer. People who eat medium-well or well-done beef are more than three times as likely to suffer stomach cancer as those who eat rare or medium-rare beef.

What Can You Do?

If you’re looking to reduce your risk of cancer, here are some tips:

  • Stick to medium-rare or rare when cooking beef, lamb, pork, fish and poultry.
  • Try other sources of protein like milk, eggs, tofu, and organ meats such as liver, which have very little or no HCA content.
  • If you’re charring your steak, try to keep it to a minimum.

Cooking Meat: The Link to Neurological Disorders

What is Harmane?

Harmane is a β-carboline alkaloid found in meats. It’s been nicknamed the “tremor inducer” because it’s been found in higher concentrations in people with essential tremor than in those without.

How Does it Form?

Harmane is formed when meat is cooked, especially when it’s cooked for a long time and exposed to high temperatures. So if you’re looking to avoid it, here’s what you need to do:

  • Keep cooking times short
  • Avoid high temperatures

What About Meat Consumption?

It turns out that there’s no direct correlation between how much meat you eat and how much harmane is in your blood. So it looks like it’s not just about how much you eat, but how you cook it.

Understanding Dietary Exposure to Heterocyclic Amines

What are Heterocyclic Amines?

Heterocyclic amines (HCAs) are chemicals that form when meats are cooked at high temperatures. They’re found in pan-fried, baked, grilled, and barbecued meats.

How Can We Measure HCA Exposure?

In the past, many studies used the intake level of meats cooked with high temperature cooking methods as a measure of HCA exposure. But since the level of HCAs in cooked meats depends on the temperature and length of time that meats are cooked, these studies weren’t very accurate.

More recent studies have tried to take into account cooking methods and doneness levels when estimating HCA exposure. Some studies used color photographs of cooked meats to standardize the assessment of preferred meat doneness levels.

What Does the Research Say?

Recent research suggests that usual intake levels of HCAs can be measured using food frequency questionnaires in epidemiologic studies. Here’s a quick overview of what the research says:

  • A study by Kobayashi et al (2007) found that the level of HCA exposure estimated using food frequency questionnaire data was moderately correlated with that measured in hair samples.
  • Augustsson K, (1999) found no significant association between HCA exposure and risk of bladder and kidney cancer.
  • Kampman E, (1999) found a suggestive interaction between mutagen index and NAT2 genotype.
  • Sinha R, (2002) found that well-done red meat intake was associated with an increased risk of colorectal cancer.
  • Cross AJ, (2005) found that well-done meat intake was associated with an increased risk of pancreatic cancer.
  • Sinha R, (2009) found that well-done meat intake was associated with an increased risk of prostate cancer.
  • Sinha R, (2009) also found that well-done meat intake was associated with an increased risk of bladder cancer.
  • Sinha R, (2009) also found that well-done meat intake was associated with an increased risk of esophageal cancer.

So, it looks like eating well-done meats cooked at high temperatures may increase your risk of certain types of cancer. If you’re concerned about your HCA exposure, it might be a good idea to opt for lower-temperature cooking methods like steaming or boiling.

The Scoop on Colorectal Cancer

What is Colorectal Cancer?

Colorectal cancer is a type of cancer that affects the colon and rectum. It’s one of the most common types of cancer, and it can be deadly if not caught and treated early.

What the Studies Say

Turns out, there’s been a lot of research done on colorectal cancer. Here’s the scoop:

  • Seven studies have looked into the link between colorectal cancer and well-done meat intake and HCA exposure (Augustsson et al, 1999; Kampman et al, 1999; Le Marchand et al, 2001; Nowells et al, 2002; Butler et al, 2003; Murtaugh et al, 2004; Navarro et al, 2004).
  • Most of the studies found some evidence that well-done meat and HCA exposure might be linked to an increased risk of colorectal cancer.
  • In one study, people with certain NAT2 genotypes who ate well-done meat had a 3x higher risk of colon cancer (Le Marchand et al, 2001).
  • Other studies found a moderate to strong link between well-done meat intake and certain HCAs, like MeIQx, DiMeIQx and PhIP (Nowell et al, 2002; Butler et al, 2003).
  • Even studies on colorectal polyps (precursors of colorectal cancer) found a positive association between polyps and well-done meat and/or HCA exposure (Probst-Hensch et al, 1997; Sinha et al, 1999; Sinha et al, 2001; Ishibe et al, 2002; Tiemersma et al, 2004; Gunter et al, 2005; Sinha et al, 2005; Wu et al, 2006; Shin et al, 2007a; Shin et al, 2007b).

The Bottom Line

The bottom line is that there’s a lot of evidence out there that suggests well-done meat and HCA exposure might be linked to an increased risk of colorectal cancer. So if you’re looking to reduce your risk, it might be a good idea to cut back on your well-done meat consumption.

The Link Between Well-Done Meat and Breast Cancer Risk

Studies Show a Connection

Turns out, if you like your steak well-done, you might want to rethink that. Three studies have looked into the connection between eating high-temp cooked meat and breast cancer risk. Here’s what they found:

  • A small hospital-based case-control study found a link between well-done meat and breast cancer risk (De Stefani et al, 1997).
  • A case-control study among postmenopausal Iowa women showed a highly significant dose-response relationship between meat doneness score and breast cancer risk (Zheng et al, 1998). Women who ate well-done meat had a 4.6-fold increased risk of breast cancer.
  • Dietary exposure levels of major HCAs were estimated (Sinha et al, 2000b). A clear dose-response relationship was observed for the risk of breast cancer with exposure to PhIP, but not other HCAs.

Genetic Factors May Play a Role

It gets worse. The study also suggested that the link between well-done meat and breast cancer risk may be influenced by genetic polymorphisms in certain genes. So if you’re genetically predisposed to breast cancer, you might want to stay away from that well-done steak.

The Bottom Line

If you’re trying to reduce your risk of breast cancer, it’s probably best to avoid eating well-done meat. And if you’re genetically predisposed to breast cancer, it’s probably best to avoid it altogether.

Cooking Meat at High Temperatures and Prostate Cancer Risk

What the Studies Say

It’s no secret that cooking meat at high temperatures can be a major risk factor for prostate cancer. But what does the research say? Here’s what four studies have to say about it:

  • Cross et al (2005) studied almost 30,000 adult men and found that eating a lot of red or white meat wasn’t linked to an increased risk of prostate cancer. But they did find a clear link between eating very well-done meat and exposure to PhIP.
  • Norrish et al (1999) conducted a cohort study in the US and found a positive association between eating well or very well-done meat and prostate cancer risk.
  • Rovito et al (2005) conducted a case-control study in New Zealand and found a positive association between eating well-done beefsteak and prostate cancer risk, but no link between HCA exposure and prostate cancer risk.
  • Koutros et al (2008) conducted a small hospital-based case-control study and found no association between HCA exposure or well-done meat intake and prostate cancer risk. But this study had some major potential biases, so take it with a grain of salt.

The Bottom Line

Bottom line: cooking meat at high temperatures can be a major risk factor for prostate cancer. So if you want to keep your prostate healthy, it’s best to avoid eating very well-done meat and exposure to PhIP.

The Dangers of Grilling and Barbequing Red Meat

The Risk of Pancreatic Cancer

Grilling and barbequing red meat is a delicious way to enjoy a summer cookout, but it may come with a hidden danger. Studies have shown that there may be a link between eating grilled or barbequed red meat and pancreatic cancer.

The first study, conducted in Minnesota, looked at 193 cases and 674 controls. It found that those who ate grilled or barbequed red meat had an increased risk of pancreatic cancer.

A larger study replicated these findings and found that those who ate well-done red meat and chicken were at an increased risk of pancreatic cancer.

The largest study of all looked at 33,000 people and found that men who ate red meat, cooked at high temperatures, and well or very well-done had a two-fold increased risk of pancreatic cancer.

So what’s the deal? It turns out that grilling and barbequing red meat can create carcinogens, like PhIP, DiMeIQx, and BaP. These carcinogens can increase your risk of pancreatic cancer.

So if you’re a fan of grilled and barbequed red meat, here’s what you should keep in mind:

  • Grill or barbeque your red meat at lower temperatures
  • Don’t cook it too well-done
  • Limit your intake of grilled and barbequed red meat

Conclusion

In conclusion, Heterocyclic amines (HCAs) are a group of carcinogenic compounds found in cooked meats, and can increase the risk of developing certain cancers. It’s important to be aware of the potential risks associated with consuming cooked meats, especially those cooked at high temperatures and for long periods of time. If you’re looking for a safer way to enjoy your favorite dishes, why not give sushi a try? Not only is it delicious, but it’s also a much healthier option.

Joost Nusselder, the founder of Lakeside Smokers is a content marketer, dad and loves trying out new food with BBQ Smoking (& Japanese food!) at the heart of his passion, and together with his team he's been creating in-depth blog articles since 2016 to help loyal readers with recipes and cooking tips.