Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53?913 ± 4000.58 (mg·min)/dL vs 42?003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.
The mechanism suggested in the study by Gul et al claiming that aspartame might prevent weight loss is simply not biologically plausible. After ingestion, aspartame is quickly digested into aspartic acid and phenylalanine (amino acids) and a small amount of methanol. It is well documented that both aspartic acid and phenylalanine are in the same form as when absorbed into the body from natural food sources such as meat or dairy products. Also, the amounts of phenylalanine from aspartame breakdown is much lower than those obtained from many other natural dietary sources. Therefore, the claims that the aspartame breakdown product phenylalanine interferes with the action of an enzyme previously shown to prevent metabolic syndrome in mice simply do not apply to humans, who consume a variety of foods that contain much higher amounts of the amino acid phenylalanine. For more information please read the ISA comments by clicking here.