(Looking at the Science on Raw vs. Cooked Foods--continued, Part 1D)
Maillard molecules and heterocyclic amines:
realistically assessing the risks
Do Maillard products carry potential risks
for mutagenicity and carcinogenicity? |
The relationship between mutagenicity and carcinogenicity.We shall see that Maillard molecules are the precursors of heterocyclic amines, which form in meat and fish cooked at high temperatures. These latter compounds are known to be mutagenic, but whether they are carcinogenic (might induce cancers) in humans using normal methods of cooking is controversial.
Let's recall here how mutagenicity and carcinogenicity relate to one another. A carcinogen is a substance that promotes the disease called cancer. A mutagen is a substance that promotes mutations (modifications of the DNA). A mutation may or may not cause cancer. (Cancer is a multi-stage process that involves much more than a single mutation; DNA can be repaired; and many more mutations affect non-coding portions of the DNA than those that govern phenotype/physiological functioning.) In fact, it is natural for some mutations to occur: at modest levels they are what drive the evolutionary process. Some mutagens are not carcinogens. Almost all known carcinogens are mutagens, but not all, because some substances can have growth-promoting activities, or be involved in non-mutational events in the development of a tumor.
Mutagenicity gauged experimentally in single-celled organisms. So, since the two concepts are distinct, and carcinogenicity is usually of most direct concern to human health, why bother studying mutagenicity? The answer is that the two concepts are correlated, and the latter can be studied and quantified much more easily and quickly, in test tubes, in single-celled organisms such as bacteria, whereas the very notion of cancer only makes sense for multicellular organisms and takes much longer to develop.
We'll also see that the Maillard molecules themselves are not carcinogenic--in fact, they appear to have anticarcinogenic effects. Finally, we mention that many factors in diet may influence, in either direction, the onset and development of cancer. Looking at any one factor in isolation may mean little without also evaluating its relationship to, and potential influence on, other factors in the overall mix.
Mutagenicity and heterocyclic amines
The formation of heterocyclic amines, which involves the Maillard reaction, is thought to require three classes of precursors: creatine or creatinine, free amino acids or dipeptides, and sugar [Skog 1993, 1995]. Creatine and creatinine are present mostly in meat and fish.
Mutagens in meat are usually produced (in parts per billion) in the crust during frying, broiling, and baking [Jagerstad et al. 1991]. Another important source is meat extracts, consumed as gravies and meat bouillons. Mutagenicity increases with temperature and with cooking time. Patties made of bovine (cow) muscle or tongue were not significantly mutagenic when fried at 150°C (302°F) for 3 minutes each on both sides [Jagerstad et al. 1991, pp. 92-93].
An experiment by Knize et al. [1994] on fried beef patties showed that the increase in PhIP and MeIQ formation (two heterocyclic amines) is exponential over the range 0 to 11 minutes and 150° to 230°C (302° to 446°F), which might be a good argument in favor of raw or rare meat versus well-done. The table below presents some examples of cooked foods with their PhIP and MeIQx contents (which account for a large part of cooked-food mutagenicity).
AMOUNTS OF HETEROCYCLIC AMINES
IN SELECTED COOKED MEATS
Figures are in nanograms of heterocyclic amine per gram of food.
(Note: a result of zero means "undetectable" amounts.)
|
FOOD / Method of Preparation
|
PhIP
|
MeIPx
|
Total HCAs
|
Information Source
|
| Well-done flame-grilled chicken breast |
?
|
?
|
> 300
|
Knize MG, et al. 1997
|
| Well-done grilled chicken |
226
|
?
|
?
|
Holder CL, et al. 1997
|
| Fried fish |
69.2
|
6.44
|
?
|
Zhang XM, et al. 1988
|
| Very well-done oven-broiled bacon |
30.3
|
4
|
?
|
Sinha R, et al. 1998
|
| Pan-fried very well-done sausage |
?
|
5.4
|
?
|
Sinha R, et al. 1998
|
| Sausage links |
?
|
1.3
|
?
|
Sinha R, et al. 1998
|
| Broiled pork chops |
?
|
0
|
?
|
Sinha R, et al. 1998
|
| Hot dogs |
0
|
0
|
0
|
Sinha R, et al. 1998
|
| Ham slices |
0
|
0
|
0
|
Sinha R, et al. 1998
|
| Microwave-cooked hamburger |
0
|
0
|
0
|
Holder CL, et al. 1997
|
From Sugimura et al. [1990], the mutagenicity of heterocyclic amines has been tested on the two strains TA98 and TA100 of the Salmonella bacteria. The results, compared with Aflatoxin B1 (a mutagen present in some molds) and benzo(a)pyrene (a polycyclic aromatic hydrocarbon, or PAH--more later) are shown in the table below.
Results were obtained by using the Ames assay (http://embryo.ib.amwaw.edu.pl/~dslado/invittox/prot/30.htm), which is a standard test to measure the mutagenicity of chemicals on certain strains of bacteria. These bacteria (e.g., Salmonella TA98 or TA100) have been selected (bred) to require histidine (for growth). After a standard time (48 hours) at a standard temperature (37°C=98.6°F), the number of "revertants" (bacteria which mutate back to a non-histidine-requiring state) is measured.
MUTAGENICITY OF HETEROCYCLIC AMINES
in TA98 and TA100 Salmonella
Figures in the table are expressed in number of revertants per microgram.
(Higher figures represent greater levels of mutagenicity.)
|
Substance | Source
|
Mutagenicity on Salmonella
|
|
TA98
|
TA100
|
|
HETEROCYCLIC AMINES
|
| IQ |
Broiled sun-dried sardine |
433,000
|
7,000
|
| MeIQ |
Broiled sun-dried sardine |
661,000
|
30,000
|
| IQx |
Fried meat |
75,000
|
1,500
|
| MeIQx |
Fried beef |
145,000
|
14,000
|
| 4,8-DiMeIQx |
Heated mixture of creatinine, threonine, and glucose |
183,000
|
8,000
|
| 7,8-DiMeIQx |
Heated mixture of creatinine, glycine, and glucose |
163,000
|
9,900
|
| PhIP |
Fried beef |
1,800
|
120
|
| Trp-P-1 |
Tryptophan pyrolysate |
39,000
|
1,700
|
| Trp-P-2 |
Tryptophan pyrolysate |
104,200
|
1,800
|
| Glu-P-1 |
Glutamic acid pyrolysate |
49,000
|
3,200
|
| Glu-P-2 |
Glutamic acid pyrolysate |
1,900
|
1,200
|
| Phe-P-1 |
Phenylalanine pyrolysate |
41
|
23
|
| A(alpha)C |
Soybean globulin pyrolysate |
300
|
20
|
| MeA(alpha)C |
Soybean globulin pyrolysate |
200
|
120
|
|
FOR COMPARISON
|
| Aflatoxin B1 |
-- |
6,000
|
2,800
|
| Benzo(a)pyrene |
-- |
320
|
600
|
As seen from the above, some compounds are potent mutagens in Salmonella. The specific mutagenic activity of PhIP is relatively low, but the content of PhIP in food is more than 10 times higher than those of other heterocyclic amines. It is thought that the main food mutagens are MeIQx, PhIP, DiMeIQx, and IQ [Augustsson 1997, Johansson 1994, Zhang 1988].
However, in contrast with heterocyclic amines' potent mutagenicity in Salmonella, they are, surprisingly, only moderately carcinogenic on rats and mice. Each heterocyclic amine has one or more specific target organs (e.g., liver, colon, breast, etc.). [See also Knasmuller 1992, Nagao 1993.]
GO TO NEXT PART OF ARTICLE
(Heterocyclic Amines and Cancer Risk: Lab vs. Real-World Conditions)
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SEE REFERENCE LIST
SEE TABLE OF CONTENTS FOR: PART 1 PART 2 PART 3
GO TO PART 1 - Is Cooked Food "Toxic"?
GO TO PART 2 - Does Cooked Food Contain Less Nutrition?
GO TO PART 3 - Discussion: 100% Raw vs. Predominantly Raw
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