Japanese Natto has a Binding Activity to Mutagenic-Carcinogenic Heterocyclic Amines


When muscle meats, such as beef, pork, fowl, and fish, are cooked at high temperatures, heterocyclic amines (HCAs) are formed in and on the food.  Some HCAs found in cooked and especially burned meat are known carcinogens.

These HCAs form when amino acids, creatine and monosaccharaides (sugars) react at high cooking temperatures.  Cooking methods such as frying, grilling and barbequing tend to form the highest levels of HCAs. 

HCAs are found in meats that are cooked to the well done stage, in pan drippings, and in meat surfaces that show a crispy brown crust.  HCAs usually form when these muscle meats are cooked either at high temperatures (125-300o C or 275-572o F) or cooked for long periods of time.


Heterocyclic Amines forms when beef is barbequed

Researchers have identified up to 20 HCAs that may pose human cancer risk.  1   Four individual HCAs are listed in the Report on Carcinogens as reasonably anticipated to be a human carcinogen.  These 4 HCAs are as follows:

  • 2‑Amino-3,4-dimethylimidazo[4,5‑f]quinoline (MeIQ)
  • 2‑Amino-3,8-dimethylimidazo[4,5‑f]quinoxaline (MeIQx)
  • 2‑Amino-3-methylimidazo[4,5‑f]quinoline (IQ)
  • 2‑Amino-1-methyl-6-phenylimidazo[4,5‑b]pyridine (PhIP)

The toxicity of these HCAs is quite potent.  The most potent of the 4 widely studied HCAs is MelQ.  MeIQ is almost 24 times more carcinogenic than aflatoxin, a carcinogen produced by mold.  2  All the 20 HCAs are more toxic than benzopyrene, a carcinogen found in cigarette smoke and coal tar.  3

There are a number of epidemiological studies that show associations between the consumption of HCAs and certain cancers.  4  The identified cancers are as follows:

  • Breast cancer
  • Colorectal cancer
  • Esophagus cancer
  • Lung cancer
  • Pancreatic cancer
  • Prostate cancer
  • Rectum cancer
  • Stomach cancer

The U.S. Department of Health and Human Services released the 13th Report on Carcinogens on October 2, 2014.  In this report, researchers indicated that the dietary exposure to HCAs has been estimated at 1-17 ng/kg bodyweight per day.  5

The Table below shows the average daily lifetime consumption of HCAs for subgroups of the U.S. population.  This analysis was based on the food intake data of 27215 people participating in the 1994 to 1996 Continuing Survey of Food Intakes by Individuals (CSFII) survey. Approximately 16 percent of HCA exposure came from hamburgers.

Table: Lifetime average weighted intake of four HCAs by men and women in the U.S.  6  7
HCA type Lifetime average intake – All, ng/day Lifetime average intake – All men, ng/kg/day
PhIP 6.0 6.2
MeIQx 1.1 1.2
DiMeQx 0.20 0.21
IQ 0.23 0.18

Detoxifying and Minimizing the Risks of Carcinogenic HCAs

A study from October 2001 published in the Canadian Journal of Microbiology, entitled, “Binding activity of natto (a fermented food) and Bacillus natto isolates to mutagenic-carcinogenic heterocyclic amines”, found that the fermented food Natto is able to scavenge dietary mutagenic heterocyclic amines through binding.



The mutagenic heterocyclic amines used were:

  • Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole)
  • Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole)
  • Glu-P-1 (2-amino-6-methyldipyrido(1,2-a:3’2′-d)imidazole)
  • PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine)
  • IQ (2-amino-3-methylimidazo(4,5-f)quinoline)
  • MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoxaline)
  • MeIQx (2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline)
  • MeAalphaC (2-amino-3-methyl-9H-pyrido(2,3)indole)

The Natto and other fractions of Natto exhibited high binding activity towards:  8

  • Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole)
  • Trp-P-2 (3-amino-1-methyl-5H-pyrido(4,3-b)indole)
  • PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine)
  • MeAalphaC (2-amino-3-methyl-9H-pyrido(2,3)indole)

However, the Natto did not effectively bind with:

  • Glu-P-1 (2-amino-6-methyldipyrido(1,2-a:3’2′-d)imidazole)
  • IQ (2-amino-3-methylimidazo(4,5-f)quinoline)
  • MeIQ (2-amino-3,4-dimethylimidazo(4,5-f)quinoxaline)

In addition to Natto having the ability to bind to mutagenic-carcinogenic HCAs, there are other natural substances that have been researched and studied for their ability to bind and detoxify HCAs.  These natural substances are listed in the Table below:

Natural Substances that Detoxifying and Minimizing the Risks of Carcinogenic HCA’s

Indole-3-carbinol 1
Beneficial bacteria
Bifidobacteria longum2
Lactobacillus casei DN 1140013
Cruciferous vegetables6 7
Conjugated linoleic acid8
Epigallo-Catechin-Gallate (Green tea)10

Informational References:

Substances Listed in the Thirteenth Report on Carcinogens

National Cancer Institute – Chemicals in Meat Cooked at High Temperatures and Cancer Risk

U.S. Department of Health and Human Services Public Health Service National Toxicology Program – Selected Heterocyclic Amines: PhIP, MeIQ, and MeIQx

U.S. Department of Health and Human Services Secretary – 13th Report on Carcinogens

Report on Carcinogens, Thirteenth Edition – Heterocyclic Amines (Selected)


Megumi Organic Natto

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