Acrylamide: A Review of Its Formation and Health Effects

Acrylamide: A Review of Its Formation and Health Effects Josh Lobsenz

Abstract: With the rise of genetically modified organisms and public support of food being “locally sourced”, “organic”, or “farm-to-table”, chemicals within food, such as acrylamide, have come under scrutiny. This paper will examine how acrylamide is formed in food and its potential health effects on humans.

Acrylamide is a chemical that is found in foods when cooked with certain hightemperature methods,1 such as frying and grilling. It consists of an amide whose nitrogen is bonded to two hydrogens and whose carbon is bonded to an ethene (see Figure 1 below).

Figure 1: The structure of acrylamide.2

Acrylamide is formed via the Maillard reaction. In general, a Maillard reaction consists of a reducing sugar reacting with an amino acid at a high temperature; since almost all food contains at least some sugars and protein, Maillard reactions occur when food is cooked. It can manifest itself as the browning and flavor of meat, the color of toast, and the taste and golden-brown color of fried food.3 So how does the reaction work? (In order to simplify, this paper will only discuss the Maillard reaction with regard to creating acrylamide, as Maillard reactions can produce a multitude of other compounds.) The process begins with one of a handful of amino acids: asparagine, methionine, glutamine, cystine, and aspartic acid. Of these, asparagine is most commonly referenced and results in the highest levels of acrylamide, so it will be the amino acid used in this paper’s mechanism. Asparagine reacts with a sugar’s carbonyl group, and, via dehydration, a double bond is created between the non-amidic nitrogen and the formerly carbonyl carbon, resulting in a Schiff base (see Figure 2).

Figure 2: A Schiff base.4

The Schiff base releases a carbon dioxide molecule, and the nitrogen accepts a hydrogen atom, making it positively charged; this causes the double bond and negative charge to alternative between the two carbons, creating resonance. Both forms of the molecule become acrylamide, though by different means. In one, a hydrogen shifts onto the anionic carbon, stabilizing it, breaking it off from the nitrogen, and creating acrylamide. For the other form of the resonant molecule, water enters the system and breaks it up into an aldehyde and 3aminoproprionamide; in the latter of these, the nitrogen takes a hydrogen atom from the carbon and breaks free, forming ammonia. The unstable carbon then accepts a hydride shift and forms a double bond with the adjacent carbon, creating acrylamide.5,6,7 The mechanism is shown in Figure 3. Temperature is also an important factor in the accumulation of acrylamide (see Figure 4). Acrylamide will not form below

120 degrees Celsius, and it peaks at about 170 degrees Celsius with levels around 450 milligrams per mole.8 Additionally, the longer a food is cooked at a high temperature, the more acrylamide forms.

Figure 3: The mechanism for the formation of acrylamide.9 Figure 4: Amount of acrylamide produced at different temperaturesfrom0.1mmolasparagineand0.1 mmol glucosein0.5Mphosphatebuffer.10 Aspreviouslynoted,asparagineisthe amino acid most likely to form acrylamide. However, this does not necessarily mean that foods high in asparagine have high levels of acrylamide. For instance, asparagus, the namesake of asparagine, generally has very little acrylamide,11 though this may be due to the fact that asparagus is typically steamed or boiled, cooking methods that do not result in the formation of acrylamide. The foods most mentioned as having high acrylamide levels are potatoes, particularly when they are fried at high temperatures; grains, such as cereal and toast; and coffee. Interestingly, meat does not have a lot of acrylamide, even when it is fried or burnt. (While there is concern that burnt meat can cause cancer, this is due to the formation of heterocyclic amines rather than acrylamide.12) This could be due to the fact that meat has very few sugars init.13 As a side note, potatoes are high in asparagine and carbohydrates, which explains why they have high acrylamide levels. In order to reduce acrylamide accumulation, scientists have developed genetically modified potatoes that decrease the amount of glucose and fructose in the potato. This has shown to be effective in lowering the potatoes’ acrylamide levels (see

Figure 5 below).14

Figure5:Acrylamidelevelsindifferentgenetically modified potatoes compared to the non-GMO potato.15

With all this discussion of acrylamide, what is its impact on human health? Do concerns about it have any basis in research?

The greatest worry about acrylamide is that it is carcinogenic. In studies, animals that were given higher doses of acrylamide were more likely to develop cancer. Additionally, several organizations, such as the International Agency for Research on Cancer, the United States National Toxicology Program, and the United States Environmental Protection Agency, all say that acrylamide is probably carcinogenic in humans.16 The human body converts acrylamide into glycidamide (see Figure 6), which is known to alter and damage DNA. Despite this, studies in humans have not shown that increased intake of acrylamide leads to a higher cancer risk; this could be because humans process acrylamide differently than animals or because it is harder to control and account for confounding variables in humans. The United States Food and Drug Administration has urged for more longterm studies on the toxicity of acrylamide.17

1 "Acrylamide Questions and Answers." FDA, U.S. Food & Drug Administration, www.fda.gov/food/chemicals/acrylamidequestions- and-answers. Accessed 3 May 2020. 2 "Acrylamide." Wikipedia, en.wikipedia.org/wiki/Acrylamide. Accessed 3 May 2020. 3 "What is the Maillard Reaction?" Science of Cooking, www.scienceofcooking.com/maillard _ reaction.htm. Accessed 3 May 2020. 4 Zyzak, David V., et al. "Acrylamide Formation Mechanism in Heated Foods." Journal of Agricultural and Food Chemistry, vol. 51, no. 16, 30 July 2003, pp. 4782-87, DOI:10.1021/jf034180i. Accessed 3 May 2020. 5 Mottram, Donald S., et al. "Acrylamide Is Formed in the Maillard Reaction." Nature, vol. 419, no. 6906, 3 Oct. 2002, pp. 448-49. 6 Stadler, Richard H., et al. "Acrylamide from Maillard Reaction Products." Nature, vol. 419, no. 6906, 3 Oct. 2002, pp. 449-50. 7 Zyzak, David V., et al. 8 Mottram, Donald S., et al. 9 Stadler, Richard H., et al. Figure 6: The structure of glycidamide, a mutagenic compoundwhichacrylamideconvertsinto.18

Since its discovery in food in 2002, acrylamide has been the subject of much discussion in the scientific community and concern in the general public. Even though it is formed from delicious chemical reactions, it may be harmful to humans. That being said, some reactions to it may be overstated; more research needs to be done to determine how dangerous it really is.

10 Mottram, Donald S., et al. 11 "What Is Acrylamide and How Is It Involved with Food and Health?" The World's Healthiest Foods, www.whfoods.com/genpage.php?tname=george&dbi d=260. Accessed 4 May 2020. 12 "MeatandCancer."CancerCouncil NSW, www.cancercouncil.com.au/21639/ cancer-prevention/diet-exercise/nutritiondiet/fruit- vegetables/meat-and-cancer/. Accessed 4 May 2020. 13 “Acrylamide Questions and Answers.” 14 Rommens, Caius M., et al. "Low-acrylamide French Fries and Potato Chips." Plant Biotechnology Journal, vol. 6, no. 8, Oct. 2008, pp. 843-53. 15 Ibid., 847. 16"AcrylamideandCancerRisk."AmericanCancer Society, www.cancer.org/cancer/cancercauses/acrylamide.html. Accessed 4 May 2020. 17 "Acrylamide and Cancer Risk." National Cancer Institute, NIH, www.cancer.gov/aboutcancer/causes-prevention/risk/diet/acrylamidefact- sheet. Accessed 4 May 2020. 18 Glycidamide (CAS 5694-00-8). Santa Cruz Biotechnology, www.scbt.com/p/glycidamide5694- 00-8. Accessed 4 May 2020.