Role of glutathione and cysteine in acrylamide metabolism during in vitro and in vivo digestion

Background: Acrylamide, a probable human carcinogen found in thermally processed potato products, is reactive towards amino and thiol compounds. This reactivity suggests acrylamide might react with them in the gastrointestinal tract resulting in mitigation of associated risk with acrylamide. This study investigated the impact of the thiol compounds, glutathione and cysteine, on acrylamide fate in potato chips both in vitro and in vivo. Results: Acrylamide levels in control potato chips declined significantly during simulated digestion, with 35% and 57% reductions in the gastric and in the bioaccessible fraction, respectively. Incorporating thiol compounds (1% glutathione or 0.5% cystine) lowered initial acrylamide formation (P < 0.05) but did not further eliminate acrylamide during digestion (P > 0.05). In contrast, co-digestion of potato chips with free thiols enhanced acrylamide elimination, with 0.5% cysteine or 1% glutathione achieving a 19% reduction after the oral phase. With 1% glutathione, acrylamide elimination reached 49% in the gastric phase and 70% in the intestinal phase, while 0.5% cysteine achieved 67% elimination in the gastric phase. Male C57BL/6N mice were fed diets supplemented with reformulated potato chips containing glutathione and cysteine for 7 days, and urinary biomarkers (glycidamide, AAMA, and GAMA) were analyzed. Control diets with regular potato chips led to elevated acrylamide metabolites (AAMA, GAMA), while cysteine-containing chips reduced both. Glutathione-containing chip consumption resulted in lower GAMA but higher AAMA, suggesting enhanced acrylamide detoxification. Conclusion: The reformulation of potato chips with thiol compounds, or co-consumption of thiol compounds with acrylamide-rich foods, can effectively mitigate the potential toxicological effects of acrylamide.