Aspartame brain damage in mice

See the original  Hetle & Eltervaag: 2001 thesis abstract  aspartame brain damage in mice: Sommewald 1995 study.

For thesis in Norwegian, mailed by regular mail, contact: Anne Værnes

"Cola light, one calorie" men hva med jhernen? Hovedfagoppgave hosten 2001 Utfort av Arnstein Eltervaag og Elisabeth Hetle Det medisinske fakultet Institutt for kliniske nevrofag Trondheim Norway 10.desember 2001

The 48-page thesis has 35 references, and includes an English abstract. Faculty and helpers listed in the Forword are: Ursula Sonnewald (with 134 items in PubMed since 1988, showing a distinguished research career in biochemical studies of neurotoxins-- one of her studies on aspartame, published 1995 with three partners, Tomm Muller, Geirmund Unsgard, and S.B. Peterson, is given in full at the end of this post, with 18 references, and obviously presents much the same laboratory technique as applied in 2001 in the thesis.), Hong Qu (female, and Bente Urfjell. Obviously, this team has the experience, facilities, funding, faculty support, and motivation to study the biochemistry of aspartame toxicity in detail.


Introduction: Aspartame (ASM) is a product that was originally made for diabetics, but today ASM is widely used by healthy people as an artificial sweetener in many food products.

Purpose: The main goal with this research was to see whether ASM was harmful to brain cells (cerebellar granule cells). We wanted to check if the damage to the neurons is connected to the N-methyl-D-aspartate (NMDA)-receptors on these cells.


Brain cells from 7 day old mice were used. They were cultured in 24 Petri well dishes, and different quantities of ASM were added. After 7 days, the cultures were analysed by two different tests: Lactate dehydrogenases (LDH) test, which gives a picture of cell death (LDH leakage to the medium in which the cells were cultured). 3-[4,5- dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromid (MTT) test, which can be used to analyse mitochondrial activity in living cells. To test whether the NMDA-receptor was involved in the damage done by ASM, the receptor was blocked by (±)-2-amino-5 phosphonopentanocid (AP5).


Our results showed damage/cell death from an added quantity of 0.06 mg/ml ASM each day for 4 days. As a comparison there is 0.24 mg/ml ASM in Cola Light. MTT- and LDH-tests showed damage to the neurons at an added quantity of 1.5 and 3.00 mg/ml ASM after 22 hours of incubation. The results also show that ASM is in part acting through the NMDA- receptor because AP5 reduced or blocked the damage to the granule cells.


In light of these results, our conclusion is that in order to be on the safe side, it should be warned against use of ASM as a food additive, maybe especially in products consumed by children, because NMDA-receptors and the synapses involved also are connected to learning.

[A major newspaper in Norway]

[Photo caption]


Medisinstudent Elisabeth Hetle (32) har sluttet å drikke lettbrus, mens medstudent Arnstein Eltervaag (40) aldri har drukket lettbrus.

I edited this into a fairly accurate English version:

[Caption for photo]


Medical student Elisabeth Hetle (32) has stopped using aspartame diet sodas, while fellow student Arnstein Eltervaag (40) has never used them.

You can also read this article at: [article on newspage]
Dagbladet © 2001:


NTNU: Norges teknisk-naturvitenskapelige universitet:
[English] Norwegian University of Science and Technology
NO-7491 Trondheim,
Phone.: +47 73595000,
Fax: +47 73595310
Creative, Constructive, Critical: These are the keywords in our strategy. As the name states the Norwegian University of Science and Technology, NTNU, is a centre for technological education and research in Norway, with a solid foundation in the natural sciences. This tradition is interwoven with broadly based expertise in the classical university disciplines of the humanities, medicine and the social sciences. At the same time, NTNU offers the widest range of education in art subjects; music, the visual arts and architecture, of all the universities in Norway. At NTNU we strive to encourage soaring imagination and restless curiosity. Our ambition is to promote a creative interplay between all forms of human intellectual activities, the arts, the natural and social sciences, and technology. Our interdisciplinary efforts are inspired by the consummate Renaissance man Leonardo da Vinci, who unified areas of study previously seen as distinct. NTNU is an institution that provides stimulating challenges for those who want to explore new approaches. NTNU is about leading the field.

Faculty of Medicine:
The faculty does research in all the medical disciplines: basal, paraclinical and clinical subjects. Medical technology is an important area of cooperation for the faculty. Academic posts: 146. Doctoral students: 77.

Besøksadresse: Olav Kyrres g.
3, Medisinsk Teknisk Forskningssenter
Postadresse: Medisinsk teknisk forskningssenter, N-7489 Trondheim
Tlf.: 73 59 88 59, faks:
73 59 88 65,

URSULA SONNEWALD Ph.D., Professor Dept. of Pharmacology and Toxicology,
Olav Kyrres g.3,
Norwegian University of Science and Technology,
N-7489 Trondheim Norway
phone: (+47) 73 59 04 92,
fax: (+47) 73 59 86 55,
NTNU - det medisinske fakultet Institutt for farmakologi og toksikologi

(photo) First-aid for brain cells Research at SINTEF UNIMED´s MR Centre has given us a better understanding of what takes place in brain cells when their oxygen supply is reduced or cut off. As a result of its work, the Centre has been awarded a research contract by a leading Japanese drug company. In SINTEF UNIMED´s laboratory, Ursula Sonnewald has cultivated mouse brain cells.

The MR Centre is now testing new drugs which are being developed by Yamanouchi Pharmaceuticals. The manufacturer hopes that these medicines will enable doctors to reduce brain damage in stroke patients and others who are suffering from reduced or blocked oxygen supply to the central nervous system (CNS). SINTEF UNIMED will test the new drugs by means of in vitro studies and animal tests.

A lack of oxygen in the brain can lead to lasting damage since brain cells die, and because the bodily functions that are controlled by these cells are put out of operation. Damage of this sort can occur in patients who have suffered strokes, heart failure, in newborn children with paranatal injuries and people who have been rescued from drowning.

However, cells whose oxygen supply is cut for a short period are capable of surviving for a day after they are damaged. In theory, this means that it ought to be possible to save many cells before the damage becomes permanent, if only we knew just what happens in the cells at this time.

The photomicrograph below shows a collection of nerve cells that have built up a neural network in the petri dish. In the background we can see glial support cells (astrocytes).


In collaboration with Professor Geirmund Unsgård of the University of Trondheim, Dr. Tomm Müller of Trondheim Regional Hospital and scientists from the Pharmaceutical College of Denmark, Dr. Ursula Sonnewald at the MR Centre has been studying cell cultures from mice and rats. Their studies have provided new understanding of the biochemical changes that take place during the first few hours after the oxygen supply to the brain has been cut off.

Dr. Sonnewald and her partners have demonstrated differences in mechanisms of injury in the nerve cells themselves (the neurones) and the surrounding glial cells (the astrocytes) that keep the neurones alive. For this purpose she has used a spectroscopic analysis technique that utilizes nuclear magnetic resonance (NMR). In SINTEF UNIMED´s cell experiments for Yamanouchi the effects of the drugs on injured brain cells in cell cultures are studied by means of the same technique.


A parallel study at SINTEF UNIMED is looking at the effects of drugs on the brains of living rats with the aid of NMR-based imaging. The special method that is being used in this part of the study was developed by Dr. Müller in the course of his doctoral studies, in collaboration with Dr. Olav Haraldseth and Dr. Richard Jones, both at SINTEF UNIMED. This method makes it possible to identify those regions of the CNS that undergo alterations when the blood supply to these animals' brains stops. The images also show the size of the areas involved.

When the animals are given medication, the images can show the extent to which the injuries disappear. In this way the technique can tell us whether a given drug is capable of crossing the blood-brain barrier, as it must do if it is to have its intended effect on the central nervous system.

Contact persons: Ursula Sonnewald Olav Haraldseth


(13C and 45Ca are radioactive isotopes of carbon and calcium, used to trace biochemical reactions.)

Bakken, Ingen Johanne; White, Linda R.; Aasly, Jan; Unsgård, Geirmund; Sonnewald, Ursula;
U-13C aspartate metabolism in cultured cortical astrocytes and cerebellar granule neurons studied by NMR spectroscopy.
GLIA. Wiley-Liss, Inc. 23, 271-277 1998

Bakken, Inger Johanne; White, Linda R.; Unsgård, Geirmund; Aasly, Jan; Sonnewald, Ursula
U-13C-glutamate Metabolism in Astrocytes During Hypoglycemia and Hypoxia.
Journal of Neuroscience Research. Wiley-Liss, Inc. 51, 636-645 1998

Håberg, Asta; Qu, Hong; Bakken, Inger Johanne; Sande, Leif Magne; White, Linda R.; Haraldseth, Olav; Unsgård, Geirmund; Aasly, Jan; Sonnewald, Ursula
In vitro and ex vivo 13C-NMR spectroscopy studies of pyruvate recycling in brain.
Developmental Neuroscience. S. Karger AG 20, 389-398 Basel 1998

Håberg, Asta; Qu, Hong; Haraldseth, Olav; Unsgård, Geirmund; Sonnewald, Ursula
In vivo Injection of 1-13C Glucose and 1,2-13C Acetate Combined With Ex Vivo 13C Nuclear Magnetic Resonance Spectroscopy:
A Novel Approach to the Study of Middle Cerebral Artery Occlusion in the Rat.
Journal of Cerebral Blood Flow and Metabolism. Lippincott Williams & Wilkins 18: 11, 1223-1232 Philadelphia 1998

McKenna, Mary C.; Sonnewald, Ursula; Huang, Xueli; Stevenson, Joseph; Johnsen, Svein F.; Sande, Leif M.; Zielke, H. Ronald
-a-Ketoisocaproate alters the production of both lactate and aspartatefrom U-13Cglutamate in astrocytes :
a 13C NMR study. Journal of Neurochemistry. Lippincott-Raven Publishers 70, 1001-1008 Philadelphia 1998

Sonnewald, Ursula; Sonnewald, Ursula; Akiho, Hiraku; Koshiya, Kazuo; Iwai, Akihiko
Effect of orotic acid on the metabolism of cerebral cortical astrocytes during hypoxia and reoxygenation :
an NMR spectroscopy study.
Journal of Neuroscience Research. Wiley-Liss, Inc. 51: 1, 103-108 1998

Waagepetersen, H.S.; Bakken, I.J.; Larsson, O.M.; Sonnewald, Ursula; Schousboe, A.
Comparison of lactate and glucose metabolism in cultures neocortical neurons and astrocytes using 13C-NMR spectroscopy.
Developmental Neuroscience. S. Karger AG 20, 310-320 Basel 1998

Waagepetersen, Helle S.; Bakken, Inger J.; Larsson, Orla M.; Sonnewald, Ursula; Schousboe, Arne
Metabolism of Lactate in Cultured GABAergic Neurons Studied by 13C Nuclear Magnetic Resonance Spectroscopy.
Journal of Cerebral Blood Flow and Metabolism.
Lippincott-Raven Publishers 18: 1, 109-117 Philadelphia 1998

Qu, Hong; Håberg, Asta; Sæter, Oddbjørn; Haraldseth, Olav; Unsgård, Geirmund; Sonnewald, Ursula
Pyruvate recycling.
Journal of Neurochemistry. Lippincott-Raven 71 USA, 1998

Schousboe, Arne; Gegelashvili, Georgi; Sonnewald, Ursula
Role of astrocytes in glutamate metabolism during neurotransmission.
Journal of Neurochemistry. Raven Lippincott 71 USA, 1998

Sonnewald, Ursula; Håberg, Asta; Qu, Hong; Sæter, Oddbjørn; Haraldseth, Olav; Unsgård, Geirmund
Stroke, the metabolic approach.
Journal of Neurochemistry vol. 71. Lippincott-Raven USA, 1998

(photo of woman)
Cand.scient. Hong Qu (30) fra Shenyang, Kina, har studert vekselvirkninger mellom celler i hjernen (astrocytter og nevroner) i sin doktoravhandling ved Norges teknisk-naturvitenskapelige universitet, NTNU.