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Acrylamide (2-propenamide) is a known neurotoxin[1][2] and carcinogen[3], present in heated foods (incl. bread) and cigarette smoke. Environmentally, it may be the result of decomposition of polyacrylamide (in herbicides). Acrylamide is industrially produced for various purposes (eg polymeres). It decomposes in the presence of acids, bases and oxidizing agents, rendering ammonia or nitrogen oxides. Endogenously, acrylamide is metabolized ('activated' by P450 enzymes[4]) to glycidamide (a DNA-reactive epoxide[5]).

Acrylamide formation

Amides are derivates of ammonia or (carboxylated) amines. Acrylamide is particularly formed in heated plant foods (>120°C, peaking at 150°C[6], between 160-180°C[7], or at 210°C[8]) and 25-30 minutes cooking time[9]). Acrylamide as a Maillard reaction-product is yielded by the reaction of A + B.

  • A) amino acids, particularly asparagine. Through the acrylic acid pathway, acrylamide may also be formed from glutamic acid[10], carnosine[11], aspartic acid[12] or beta-alanine.[13], or indirectly even cysteine or serine (> pyruvic acid > acrylic acid).[14]
  • B) may be carbonyls (eg yielded by lipid oxidation) or reducing sugars (sugars yielding aldehydes; such as glucose (very effectively[15]) in starches, and other aldoses, as well as ketoses and fructose)[16]. In this reaction, glucans such as glucose, starch and cellulose are interchangeable[17], but asparagine more readily reacts with glucose than > galactose > fructose[18] > sucrose[19], though others report fructose > glucose (or alpha-dicarbonyls).[20] Also potent precursors/intermediates are aminopropionamides and (to a lesser rextend[21])dicarbonyls such as glyoxal and methylglyoxal.[22]

Higher levels of reducing sugars results in higher levels of acrylamide[23], with free asparagine being the limiting factor[24], but often levels of free asparagine correlate with free glucose and fructose levels.[25] Except for lysine[26], cysteine[27] and glycine[28], the presence of other additional amino acids may increase acrylamide formation[29], or not.[30](due to competitive HCA formation)

Acrylamide can also be formed at physiological conditions (37°C, pH 7.4) when asparagine is incubated in the presence of hydrogen peroxide (H2O2), depending on incubation time and H2O2 concentration (oxidative stress, counteracted by glutathione), which allows for endogenous acrylamide formation[31], which is actually the case in mice (oxidative stress-induced)[32] Naringenin (in grapefruits, oranges[33] and tomato skin[34]), strongly inhibits acrylamide formation[35] and P450 enzymes[36][37] that activate/detoxify HCAs and polycyclic aromatic hydrocarbons.

Acrylamide activation

Genotoxicity of acrylamide depends on its activation into glycidamide.[38] Most of the acrylamide ingested with food is absorbed in humans. Glutathione prevents most of the acrylamide being converted into the reactive metabolite glycidamide.[39] Acrylamide is efficiently activated to glycidamide[40] by P450 enzymes. P450 2E1 inhibitors, such as diallyl sulfide in garlic, inhibit acrylamide to glycidamide conversion.[41] Common human viral infections may influence this metabolism.[42] Activation of acrylamide into glycidamide turns out to be significantly more effective in non-smokers than in the higher exposed smokers.[43] Transport of acrylamide in the intestine is mediated primarily by passive processes. Depletion of cellular glutathione levels may be one potential mechanism for acrylamide (geno)toxicity.[44] To what extend acrylamide may cause DNA damage is not so much related to the activity of P450 enzymes, but more so to the extend of depletion of glutathione, which increases both genotoxicity and cytotoxicity.[45]


Alternatively, in the formation of acrylamide, A) may be acrylic acid, produced from beta-alanine, aspartic acid and carnosine (directly) or from cysteine and serine (indirectly; through pyruvic acid), reacting with B) ammonia. When in B) ammonia is replaced by methylamine (creatine is a good source of methylamine), in reaction with acrylic acid this may yield N-methylacrylamide.[46] The nitrogen and the methyl groups of methylamine may also both originate from creatinine, which may produce N-methylacrylamide through the acrylic acid pathway during cooking.[47] N-methylacrylamide is activated by hepatic glutathione S-transferases [48], produces testicular atrophy[49] is neurotoxic[50][51] and increases susceptibility to acrylamide.[52] Similar to acrylamide, un-activated N-methylacrylamide by itself is not mutagenic.[53]

Acrylamide in food

Cooked foods may contain various heat-induced carcinogens and toxins, such as HCAs, oxysterols, nitroso compounds, furan, chloropropanols and acrylamide-related substances. Particularly deep-frying has great consequences, evoking various complex reactions such as oxidation, hydrolysis, isomerization, and polymerization.[54] Microwaving creates more acrylamide than roasting[55], frying and boiling.[56] Frying in sunflower oil creates more acrylamide than frying in corn oil.[57] Phenols in olive oil are not degraded during frying and inhibit acrylamide formation.[58] Frying oil by itself is not a source of acrylamide[59]; its about the heat conducted to the food. Not antioxidants in general[60], but pyridoxamine[61] (part of the vitamin B6 family) and some antioxidants (vitamin C[62], vitamin E)[63] decrease the level of acrylamide produced during food processing. Adding antioxidants to foods may increase the formation of acrylamide upon long-term heating if free sugar concentration is low and asparagine concentration is relatively high.[64] Phytic acid inhibits acrylamide formation.[65]

  • Potatoes may contain varying levels of reducing sugars, varying per season[66], as storing below 10°C increases breakdown of starch to sucrose, ultimately cleaved by acid invertase to produce glucose and fructose[67]. The mean level of acrylamide content in all (pre-fried) frozen potato products before preparation was found to be 322 μg/kg.[68] In an Iranian study, levels of acrylamide in potato products varied between 244 and 1688 mcg/kg.[69] Baking at 170°C more than doubled the acrylamide amount that formed upon frying at the same temperature, whereas at 180°C and 190°C, the acrylamide levels of chips prepared by baking were lower than their fried counterparts.[70] Elevated phenol levels in potatoes inhibit acrylamide formation[71], and potato fiber protect the small intestines against the negative impact of acrylamide.[72]
  • Potato crisps / chips; In a Polish study, potato crisps contained 770 mcg/kg.[73] A French study found on average 954 mcg acrylamide/kg in potato chips/crisps.[74] A Chinese study found on average 1548 mcg/kg in potato chips.[75] In an Egyptian study potato chips contained 1500 mcg/kg and fried potatoes 540 mcg/kg.[76] In an Austrian study potato crisps contained up to 1500 mcg/kg (median: 499 mcg/kg).[77] A Swiss study found 7000 mcg/kg in one particular brand of potato chips.[78] In a Canadian study the acrylamide concentration in potato chips varied from 106 to 4630 mcg/kg.[79] In a Spanish study acrylamide in potato crisps varied from 81 to 2622 mcg/kg (average 740 mcg/kg).[80] and in Polish studies from 376 to 2348 mcg/kg[81] and 352 to 3647 mcg/kg.[82] The highest result was 12000 mcg/kg in overcooked oil-fried chips.[83]
  • French fries fried at 150°C to 190°C for up to 10 min had acrylamide levels of 55 to 2130 mcg/kg, with the highest levels in the most processed (highest frying times/temperatures) and the most highly browned fries.[84] A Chinese study found 604 mcg/kg in fried potato.[85] A Polish study found the lowest levels in French fries collected from bars and restaurants; 401 mcg/kg.[86] From another Chines study: "French fries were found to contain 278-4518 mcg/kg. It means that the content of acrylamide in French fries is 10,000 times higher than the drinking water guideline of World Health Organization for acrylamide.[87]
  • Wheat flour may contain 1700 to 3100 mcg acrylamide /kg.[88] Gluten may contain up to 3997 mcg/kg.[89]
  • Cookies' acrylamide concentrations correspond with baking temperature and surface color. Steam-assisted baking results in lower levels.[90] low-temperature long-time pre-treatment may reduce acrylamide yield with up to 42%.[91] Cookies baked at 150°C  for 25  minutes yielded 75 mcg acrylamide /kg, compared to 236 mcg/kg in cookies baked at 240°C  for 9 minutes.[92] Cookies baked in an oven at 205°C for 11 min yielded 107 mcg acrylamide /kg.[93] A Chinese study found on average 388 mcg acrylamide /kg in biscuits.[94] The median level found in Austrian cookies was 99 mcg/kg.[95]
  • Crispbread / crackers may contain 845 mcg/kg[96], 942 mcg/kg [97], or 1480 mcg acrylamide / kg.[98] The median in an Austrian study was 69 mcg/kg.[99]
  • Bread; By increasing baking time and temperature, acrylamide content increased from 10 to 30 mcg/kg.[100] In the crust, acrylamide levels usually are over 100 mcg/kg.[101], and levels may increase 190-fold with increased temperature and baking time; the darker the crust, the more acrylamide.[102] In general, wheat bread (up to 5 mcg/kg) and rye bread (7 to 23 mcg/kg) contain relatively little acrylamide when untoasted, but toasted wheat (11 to 161 mcg/kg) and rye bread slices (27 to 205 mcg/kg) contain much more[103]; in hard-toasted bread, all asparagine had reacted.[104] More acrylamide was formed in "dark" toasted bread slices (43 to 611 mcg/kg), than "light" (8 to 218 mcg/kg) or "medium" (11 to 214 mcg/kg) toasted slices.[105] If nitrogen fertilization is applied to the wheat, the bread products may contain 55.6 mcg/kg instead of 10.6 mcg acrylamide /kg.[106] In an Egyptian study bread contributed to 17% of the mean daily dietary acrylamide intake.[107]
  • Cereals may contain from 50 to 347 mcg/kg[108], or 62 to 803 mcg/kg, 292 mcg/kg on average[109], up to 1080 mcg acrylamide /kg.[110].
  • Corn products were found to contain between 30 and 410 mcg acrylamide /kg [111]. The median level found in popcorn was 97 mcg/kg.[112] Microwaved popcorn contains less acrylamide than traditionally produced popcorn.[113]
  • Soybean-containing commercial bakery products contain higher levels of acrylamide than similar bakery products without soy.[114]
  • Coffee may contain 29 mcg/kg in coffee drink[115] 708 mcg/kg in Robusta coffee, 374 mcg/kg in Arabica coffee[116] and 2528 mcg acrylamide /kg in instant coffee.[117] The median levels found in coffee was 169 mcg/kg.[118] In another study, acrylamide levels ranged from 45 to 374 mcg/kg in unbrewed coffee grounds, from 172 to 539 mcg/kg in instant coffee crystals, and from 6 to 16 mcg/kg in brewed coffee.[119] For coffee and cacao powder, a significant decrease occurred during storage for 3 or 6 months, respectively. Acrylamide concentrations dropped from 305 to 210 microg/kg in coffee and from 265 to 180 mcg/kg in cacao powder.[120]
  • Chocolate; The acrylamide levels in chocolate varied between 23 and 537 mcg/kg.[121]
  • In prawn strips, on average 341 mcg/kg and in rice crusts 201 mcg/kg acrylamide was found. Heated protein-rich food also showed some acrylamide content, ranging from 2 to 78 µg/kg.[122] In 28 commercial precooked breaded chicken samples analyzed, acrylamide concentrations ranged between 910 and 970 mcg/kg, which may almost double during storage.[123]
  • Thai curry; Acrylamide is also formed in Thai curry cooked in coconut milk, with coconut milk being the source.[124] Antioxidants from bamboo leaves inhibit acrylamide formation.[125]
  • Almonds roasted at 138°C for 22 min had acrylamide levels ranging from 117 to 221 μg/kg, with an average of 187 μg/kg.[126] Low levels in roasted almonds (8 to 86 mcg/kg) significantly increased with increased roasting temperature and time.[127] Nuts with a lower initial moisture content will contain more acrylamide after roasting.[128] Roasted hazelnuts contained very little acrylamide because of the low content of free asparagine in the raw nut.[129]
  • Prune juice contains 186 to 916 µg/kg acrylamide. Strained prunes in babyfood may contain 75 to 265 µg/kg, baby apple/prune juice 33 to 61 µg/kg, and prunes 58 to 332 µg/kg. Prunes are produced industrially by dehydration of plums at temperatures of 85–90°C for 18 h. Prune juice is produced by boiling the prunes in water, and may include pasteurisation. Strained/pureed prunes in babyfoods contain up to 265 mcg/kg acrylamide, and apple-prune juice up 61 mcg/kg.[130]
  • Infant powdered milk and baby foods in jars contained 3.01 to 9.06 mcg acrylamide /kg and 6.80 to 124.93 mcg/kg respectively.[131] Ready to eat baby foods; gruel (1.4 mcg/kg), porridge (26 mcg/kg) and canned baby food (7.8 mcg/kg) all contained acrylamide.[132]
  • Sulfurized apricot (and other dried fruits[133]) also contains acrylamide. During storage, acrylamide content may decrease by 53%.[134]
  • Black olives (cured, commercial) contain acrylamide as well.[135]
  • Drinking water may contain very little acrylamide; < 0.03 mcg/L.[136]

Acrylamide food additives

  • AF-2 or furylfuramide; 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (widely used in Japan[137]), was first demonstrated to be mutagenic in Escherichia coli WP-2 and then proved to be carcinogenic in experimental animals [138][139][140] 5-nitro-2-furyl is a radical.
  • 5-NFAA; 3-(5-nitro-2-furyl)acrylic acid proved to be more mutagenic than AF-2.[141]

Acrylamide exposure

Acrylamide from food given to humans is in fact absorbed from the gut. The half-live of acrylamide in the human body may vary between 2 and 7 hours.[142] Dietary protein inhibits the uptake of acrylamide, as acrylamide binds to protein, which hinders its uptake (by Caco-2 cells).[143] Dietary fiber and chlorophyllin are not protective against acrylamide toxicity.[144] Eugenol in nutmeg, cinnamon and basil restores the acrylamide-induced reduction in glutathione (similar to selenium[145]) and dopamine levels, and reduces oxidative stress in the brain.[146]

  • Though Guideline-base diets contain less acrylamide contributed by French fries and potato chips, overall acrylamide intake is yet relatively high due to more frequent breakfast cereal intake.[147]
  • In a Californian study, non-cancer benchmarks for acrylamide were exceeded by >95% of preschool-age children, most of the acrylamide coming from chips, cereal, crackers, and other processed carbohydrate foods.[148]
  • In Australia, mean daily acrylamide intake for Australians aged 2 years and above, was estimated as 0.4 to 0.5 mcg/kg bodyweight. 1.0 to 1.3 mcg/kg bw for young children (2-6 years).[149]
  • In Sweden, an average daily intake of 35 mcg corresponds to daily 0.5 mcg/kg body weight (body weight 70 kg).[150]
  • In Germany, the highest proportions of total intake of acrylamide came from the intake of commercial baby food (86-91%) in infants, and bread (18-46%), pastries (16-35%), and potato products (7-35%) in children and adolescents.[151]
  • In the U.K. daily mean adult exposure was estimated as 0.61 mcg/kg bw (high level as 1.29 mcg/kg). The daily mean adult Irish consumer exposure was estimated as 0.59 mcg/kg bw (high level as 1.75 mcg/kg).[152]
  • In Poland, the daily exposure of infants aged 6-12 months of life was estimated at minimally 0.41 to 0.62 μg/kg bodyweight (bw), averagely at 2.10 to 4.32 μg/kg bw. Worst case scenario at 7.47 to 12.35 μg/kg bw; several dozen times higher than for the average total population.[153] In another study, acrylamide intake in the children aged 7-13 was 1.78 mcg/kg and in (14 to 18 yrs) adolescents 1.17 mcg/kg bw.[154] In the total population, the estimated daily mean acrylamide exposure is 0.43 mcg/kg bw. The main sources of dietary acrylamide in Poland is bread (45%), French fries and potato crisps (23%) and roasted coffee (19%).[155]
  • In a French study mean daily acrylamide exposure was assessed to be 0.43 μg/kg of body weight for adults and 0.69 μg/kg for children.[156]
  • In Finland, the most important source of acrylamide exposure was coffee, followed by casseroles rich in starch, then rye bread. Among children, the most important sources were casseroles rich in starch and then biscuits and, finally, chips and other fried potatoes. Daily acrylamide exposure per kg bodyweight was highest among the 3-year-old children (1.01 µg/kg) and lowest among 65-74-year-old women (0.31 µg/kg).[157]
  • In Norway the estimated median dietary intake of acrylamide 13.5 microg/day in nonsmokers and 18.3 microg/day in smokers.[158] The dietary exposure of 119 pregnant women to acrylamide was estimated at 0.3 mcg/kg bodyweight.[159]
  • In The Netherlands, the mean acrylamide exposure was 0.48 mcg/kg bw. Risk of neurotoxicity is negligible. The additional cancer risk might not be negligible. For 344 food products, acrylamide amounts ranged from <30 to 3100 mcg/kg.[160]
  • In Belgium, the daily average acrylamide exposure was calculated to be 0.4 mcg/kg bodyweight, and the main contributors being chips (23%), coffee (19%), biscuits (13%), and bread (12%).[161] In another study biscuits (35.4%), French fries (29.9%), bread (23.5%), and chocolate (11.2%) were identified to be the main sources of dietary acrylamide.[162] The estimated mean dietary intake of acrylamide in Flemish adolescents was 0.51 mcg/kg bw.[163]
  • In Egypt the highest mean daily dietary intake of acrylamide (3.82 mcg/kg body weight) was for the age group from 3 to 6 years old, while the lowest acrylamide intake (0.49 mcg/kg) was that of the age group above 50 years old.[164]
  • In Taiwan, comparing 294 snack foods, the highest levels of acrylamide were found in root- and tuber-based snack foods (average 435 μg/kg), followed by cereal-based snack foods (average 299 μg/kg). Rice flour-based, seafood-based, and dried fruit snack foods had the lowest acrylamide content (average <50 μg/kg).[165]
  • In China, the estimated mean acrylamide intake is 0.28 mcg/kg bodyweight.[166]

Health effects

  • Neurotoxicity; Acrylamide induces hepatic ornithine decarboxylase (ODC)[167] and affects behaviour by influencing hepatic mechanisms or central dopaminergic function.[168] Decreased dopamine levels may be due to acrylamide induced (radical) peroxynitrite formation.[169] The nerve terminal is a primary site of acrylamide action, which impairs neurotransmitter release and promotes degeneration by inhibiting membrane-fusion processes (by adducting nucleophilic sulfhydryl groups on proteins critically involved in membrane fusion).[170] In rats, 5000 mcg acrylamide/kg induces cognitive and motivational alterations.[171] Neurotoxicity due to acrylamide is a documented effect in human epidemiological studies[172], but not likely to occur in the general population except very high consumers.[173][174]
  • Health in general; Acrylamide and its metabolite glycidamide bind with proteins to form protein adducts in metabolic processes.[175] Acrylamide increases expression of nitric oxide synthase (iNOS) and cycloogenase-2 (Cox-2) and NOS activity in breast epithelial cells.[176] These are known to be early molecular changes in disease formation. In humans, chronic ingestion of acrylamide (and trans-fatty acids) induces a proinflammatory state (increasing homocysteine and plasma C-reactive protein[177]), a risk factor for atherosclerosis.[178]
  • Pregnancy; The placenta gives negligible protection of the fetus to exposure from acrylamide[179]. The concentration of acrylamide adducts in the blood of human neonates is approximately 50% of the adduct level found in the blood of the mother.[180] In humans, maternal dietary exposure to acrylamide is associated with reduced birth weight and head circumference.[181][182] In pregnant mice, both acrylamide and fried potato chips increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown-rump length of the offspring before and after birth. Fried potato chips induced higher rates of congenital malformations than acrylamide alone.[183] In rat pups, acrylamide administration induced neurotoxic symptoms.[184] The lactational transfer of acrylamide to rat offspring is limted though (<10%).[185] In human breast milk samples (except one) the acrylamide level was below 0.5 mcg/kg.[186]
  • Intestines; In mice, acrylamide altered the morphology and histology of the small intestinal wall, decreasing proliferation, myenteron and submucosal thicknesses, villus length, fractal dimension, crypt depth, crypt number, and the small intestinal absorptive surface. Conversely, apoptosis, hemoglobin adduct levels, intensity of epithelium staining, enterocyte number, villus epithelial thickness, and crypt width and parameters associated with nerve ganglia were increased. These effects were inhibited by potato fiber.[187]
  • Reproductive toxicity; In rats, acrylamide exposure of 2500 μg/kg bodyweight caused significant changes in serum hormones, histopathology, testicular gene expression and cell proliferation[188], but no thyroid, hypothalamus or pituitary changes (hormones, mRNA levels)[189] In weaning male rats, acrylamide has a toxicological effect on the reproductive system.[190] In mice, increased fat intake potentiates acrylamide-induced oxidative stress in the epididymis and epididymal sperm and a subsequent effect on spermatogenesis.[191] Acrylamide may also affect the Leydig cells (androgen release).[192] In humans, reproductive toxicity due to acrylamide is not likely to occur in the general population except very high consumers.[193]
  • Cancer; Acrylamide is clearly carcinogenic in studies in animals, in which it causes increased tumour incidence at a variety of sites.[194] Acrylamide targets endocrine sensitive tissues, increasing DNA damage in thyroid, testicular mesothelium and adrenal medulla.[195] Acrylamide (and/or its metabolites) are genotoxic in human lymphocytes.[196] In mice, 0.14 mmol glycidamide / kg bodyweight induces DNA adduct formation[197] and DNA adducts in lymphoma cells in a linear dose-dependent manner. Glycidamide (acrylamide metabolite) is mutagenic starting at a 2mM dose.[198] In rats, at a dose of 1 μg/kg bodyweight, adducts (DNA adducts, primarily at N7 of guanine) were found in kidney and lung, but not in liver. At 10 μg/kg bw, adducts were found in all three organs, at levels close to those found at 1 μg acrylamide/kg.[199] Carcinogenicity and mutagenicity are possible hazardous health effects for the general population[200], but only with relatively high intakes.[201][202] After lifelong daily exposure to 1 mcg acrylamide per kg body weight, 6 out of 10,000 individuals may develop cancer due to acrylamide.[203] Human epidemiological studies show a lack of relationship between acrylamide intake and various types of cancer.[204][205]] Glycidamide is only moderately genotoxic.[206] Given the consistent relationship between dietary carcinogenic heterocyclic amines (HCAs) and various types of cancer, and that dietary acrylamide mainly comes from processed plant (starchy) foods, and that dietary carcinogenic HCAs mainly come from processed animal foods, a high plant food intake (vs high animal food intake) is indeed unlikely to increase exposure to dietary carcinogens (acrylamide intake will be at the expense of HCA intake).


Aminopropionamides are biogenic amines of asparagine. Aminopropionamide (APA), 3-aminopropionamide (3-APA) and 3-(alkylamino)propionamides (benzyl, phenylethyl, butyl, and octyl) may all be precursors of acrylamide[207] through diverse pathways.[208] 3-Hydroxypropanamide is (in reaction with asparagine) the least potent precursor of acrylamide.[209] 3-APA may form at >130°C[210] 3-APA has a >12-fold higher efficacy in acrylamide generation than asparagine.[211] In the absence of carbohydrates, 63 mol% of 3-APA was converted into acrylamide (at 170°C).[212] 3-APA inhibits the enzyme diamine oxidase[213] and may be formed through different pathways:

  • 1) from asparagine reacting with glucose or 2-oxopropionic acid [214](or other reducing sugars),
  • 2) by decarboxylation of asparagine by lipid oxidation products (particularly alkadienals and analogous ketodienes, hydroperoxides and alkenals)[215] or
  • 3) by enzymatic decarboxylation of asparagine; 3-APA is formed during storage of intact potatoes (20° or 35°C) or after crushing of the cells.[216].

3-APA is present in Gouda cheese; increasing to 1300 mcg/kg after thermal processing.[217] Wheat flour containing high levels of asparagine will yield high levels of both acrylamide and 3-APA.[218] Wheat flour may contain 40 to 76 mg of 3-APA / kg.[219] Pyridoxamine (part of the vitamin B6 family) induces 3-APA formation at the expense of acrylamide formation.[220]



Author of this article is Thijs Klompmaker, born in 1966