Aspartame Guilty (Again), This Time for Weight Gain

A new study from the Massachusetts General Hospital says Aspartame may retard weight loss because it blocks the function of an enzyme vital for the prevention of obesity, type 2 diabetes and cardiovascular disease.

Dec. 29, 2016
By Stav Dimitropoulos

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Aspartylphenylalanine-methyl-ester, or Aspartame, is the by-prod­uct of an ulcer drug exper­i­men­ta­tion back in 1965, when a com­pany chemist found an inter­me­di­ate chem­i­cal to have a par­tic­u­larly sweet taste. About a decade later, Aspartame was approved by the FDA for restricted use in dry foods. Then it got on an exper­i­men­tal roller coaster of bans and re-approvals.

Today, Aspartame is a dietary hot potato.” Still in wide­spread use by weight-con­scious con­sumers, Aspartame has fer­vent fans but has not escaped the heavy crit­i­cism of sci­en­tific cir­cles, who asso­ciate it with headaches, mem­ory loss, seizures, vision loss, dia­betes, Alzheimer’s, chronic fatigue and depres­sion, even can­cer.

We stud­ied the impact of Aspartame on IAP and found it can indeed pre­dis­pose to obe­sity and dia­betes.- Konstantinos Economopoulos, Researcher

A new study from the Massachusetts General Hospital (MGH) comes to fur­ther dis­tress the weight-con­scious group of peo­ple who use Aspartame as a sugar sub­sti­tute: Aspartame might actu­ally pro­hibit weight loss.

The report, Inhibition of the gut enzyme intesti­nal alka­line phos­phatase may explain how Aspartame pro­motes glu­cose intol­er­ance and obe­sity in mice,” was pub­lished in Applied Physiology, Nutrition and Metabolism. It found that Aspartame may not pro­mote weight loss because it blocks the func­tion of an enzyme vital for the pre­ven­tion of meta­bolic syn­drome (a group of symp­toms asso­ci­ated with type 2 dia­betes and car­dio­vas­cu­lar dis­ease).

Indeed, our study con­firms the obser­va­tion made by sci­en­tists in the late 1960s, that pheny­lala­nine (PHE) – a break­down prod­uct of Aspartame – specif­i­cally inhibits the action of intesti­nal alka­line phos­phatase (IAP),” said Konstantinos Economopoulos, Senior Research Scientist at the Organ Engineering and Regeneration Laboratory of the ‎Massachusetts General Hospital, and researcher of the same study.


IAP is an enzyme, and when a sub­strate mol­e­cule inter­acts with the active site of IAP, an enzyme-sub­strate com­plex is formed and the enzyme is acti­vated. Thus, the enzyme and sub­strate are said to fit together and func­tion as a lock and a key. When pheny­lala­nine inter­acts with the IAP-sub­strate com­plex, it inac­ti­vates it by pro­duc­ing a more ther­mo­dy­nam­i­cally sta­ble IAP-PHE-sub­strate com­plex. The way you can pic­ture this is like the lock, the IAP, after the addi­tion of pheny­lala­nine can­not be opened any­more with the same key-sub­strate, because there is another key behind the door, pheny­lala­nine.”

Previously the team had found that feed­ing IAP to mice kept on a high-fat diet pre­vented the devel­op­ment of meta­bolic syn­drome and reduced symp­toms in ani­mals already inflicted with the con­di­tion. The knowl­edge that pheny­lala­nine impedes the action of IAP, and the fact that the for­mer is pro­duced upon Aspartame’s diges­tion urged the researchers to inves­ti­gate whether Aspartame might actu­ally retard weight loss.

The team fol­lowed four groups of mice for 18 weeks. Two groups were kept on a nor­mal diet, one on water with Aspartame, and the other on plain water. The other two groups were fed a high-fat diet, as well as Aspartame-infused or plain water.

The study found that the high-fat diet mice that received Aspartame gained more weight than those on the same diet that received plain water while the dif­fer­ence between the weights of the two groups fed a nor­mal diet was neg­li­gi­ble. What is more, Aspartame-receiv­ing mice in both diet groups were observed to have higher blood sugar lev­els than those fed the same diets with­out Aspartame, a fact that might point out glu­cose intol­er­ance. Finally, both Aspartame-receiv­ing groups had higher lev­els of the inflam­ma­tory pro­tein TNF-alpha in their blood, which reveals a kind of sys­temic inflam­ma­tion typ­i­cal of meta­bolic syn­drome.

What do these find­ings sug­gest for one of the most com­mer­cial (at least until ste­via) and con­tro­ver­sial arti­fi­cial sweet­en­ers? Can we imply that the ongo­ing anti-Aspartame polemic will ren­der it a sweet­ener of the yore?

We have no idea about whether sub­stances like Aspartame will get banned,” answered Economopoulos. They are in wide­spread use and gen­er­ally con­sid­ered safe for human con­sump­tion. We stud­ied the impact of Aspartame on IAP and found it can indeed pre­dis­pose to obe­sity and dia­betes.”

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