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Fyrir þá sem hoppa hæð sína vegna nýlegs mats EFSA á Aspartam ættu kanski að takaþann faktor inn í myndina að matið er mest megnis byggt á rannsóknum og öryggisprufunumsem fjármagnaðar hafa verið, ýmist beint eða óbeint, af þeim fyrirtækjum sem framleiðasætuefnið umdeilda. Það fyrsta sem mér var kennt í áfanga um rannsóknaraðferðarfræði í Hívar að gera skuli góðan greinarmun á rannsóknum fjármögnuðum af háðum aðilum annars

vegar og óháðum aðilum hins vegar. Hér að neðan mun ég taka saman rannsóknir sem gefavísbendingar um meint skaðsemisáhrif Aspartams.

 Áhrif iðnaðarins á opinberar stofnanir og reglugerðir þeirra er eitthvað sem við ættum aðþekkja vel úr okkar daglega lífi enda líður varla sá dagur sem ekki fréttist af "vinskap"þessara tveggja arma ríkis og iðnaðar. Við þurfum ekki að fara mikið lengra en út fyrir litlueyjuna okkar til þess að sjá að spilling þrífst í opinberum stofnunum og aðhagsmunaárekstrar ráðgefandi nefnda og embætta við "auðvaldið" virðast óumflýjanlegir. Égætla ekki að kafa eitthvað sérstaklega djúpt ofan í Aspartam hér, þó saga þess sé ansiskrautleg, og ætla því frekar að leyfa heimildunum hér að neðan að tala sínu máli.

Með þessari yfirlýsingu tekst EFSA að skella allri ábyrgðinni á einstaklinginn ogneytendasamfélagið með því að gefa villandi skilaboð. Að lýsa einhverju yfir sem "SAFE", ánþess að taka það sérstaklega fram að þó séu takmarkanir á þeirri fullyrðingu mætti teljastóábyrgt, en hámarksþröskuldur daglegrar neyslu miðast við 40mg/kg, þ.e. 40 mg afsætuefninu sívinsæla á hvert kg af líkamsþyngd einstaklings samkvæmt skýrslunni. (FDAgerir ráð fyrir 50 mg/kg, hvað ætli útskýri muninn?) Hvaða skilaboð fær sá sem skoðar ekkismáa letrið? Gæti sá sem las bara fyrirsögnina tekið þessu þannig að fyrst Aspartam séöruggt að þá hljóti að vera í lagi fyrir t.d. barn að innbyrða efnið daglega án takmarkana?

Óháðar rannsóknir hafa aftur á móti, eins og sjá má í heimildarskránni, metið þessi mörkmun lægri vegna eitrunareiginleika þeirra efna sem brotna niður, en það eru fenylalanín(50%), aspartínsýra (40%) og metanól (10%). Við frekara niðurbrot losnar síðan umformaldehýð (viðurkennt sem krabbameinsvaldur) og maurasýru (viðurkennt sem taugaeitur).Vert er að nefna að vitaskuld finnast þessi efni mun víðar í fæðuvali og sum hver innihaldasýrur sem gagnast líkamanum til ýmissa hluta (bæði nauðsynlegar amínósýrur ogónauðsynlegar amínósýrur), en fókusinn í þessu tilfelli snýr að því hvernig einkennieitrunaráhrifa eru alltaf tengd magni hvers tiltekins efnis; snefilmagn hefur þannig minnieiturhrifandi verkanir en mikið magn við inntöku. Mikil innbyrðing efnisins til lengri tíma ættiþví alla jafna að geta leitt til krónískra vandamála, en sú þumalputtaregla á við um öll þau

efni sem hafa mældar eiturhrifandi verkanir (þ.e. öll efni í vissu magni). Eldur mætti teljastöruggur ef maður sveiflar hendinni í gegn um bálið, en ef maður heldur henni of lengi inn íeldinum að þá mun sá hinn sami mynda brunasár sem verða verri eftir því hversu mikið oglengi snertingin/efnaskiptaferlið á sér stað.

Vísindalegar rannsóknir fela aldrei í sér neina fullmótaða og endanlega niðurstöðu. Þessvegna er mikilvægt að taka einnig tillit til neytandans í þessu samhengi. Sumir einstaklingarfinna fyrir skammtímaáhrifun, t.a.m. höfuðverkjum, sjóntruflunum, breytingum í blóðþrýsting,athyglisbresti, kvíða og hjartsláttartruflunum eftir að hafa neytt varnings sem inniheldur Aspartam, en svo eru aðrir einstaklingar sem finna ekki fyrir neinum áhrifum. Ekki má svogleyma því að þær vörur sem innihalda sætuefnið aspartam geyma alltaf í sér enn fleiri gervi

og aukaefni (Acesulfame K, Potassium benzonate, kaffín, ýmis litarefni etc) og að helstu

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gagnrýnisraddir á hin ýmsu gervisætuefni, bragðefni og litarefni snúa að áhyggjum umafleiðingar til langs tíma fremur en til skamms tíma.

 Á meðan tíðni hinna ýmsu sjúkdóma fer sífellt hækkandi á meðan sífellt fleiri "óæskilegar"afurðir streyma inn á markaðinn hvort sem það sé í formi matvæla, lyfja eða mengandi

iðnvarnings, að þá hlýtur að teljast skiljanlegt að vaxandi gagnrýni í almenningssamfélaginuvegna hagsmunaárekstra milli framleiðslufyrirtækja og opinberra eftirlitsstofnanna séviðvarandi. Það gefur auga leið að með sífellri aukningu af nýjum verksmiðjuframleiddumefnasamsetningum, sem mannkyn hefur aldrei áður í sögunni komist í snertingu við, að þá séþróunarfræðilegur, líffræðilegur og taugafræðilegur fótur fyrir þeirri kenningu að þessarbreytur haldist í hendur; þ.e. aukin tíðni torskiljanlegra einkenna og sjúkdóma annars vegarog aukning „framandi“ og ónáttúrulegra iðnframleiddra afurða sem ýta undir aukið efnaáreiti ímannflórunni hins vegar.

Punkturinn með þessari færslu er tvíþvættur. Annars vegar, að einmitt í ljósi þess að viðerum sífellt að komast í snertingu við fleiri verksmiðjuframleidd/framandi efni sem í mörgum

tilfellum er lítið vitað um, að þá er ábyrgð þessara opinberu eftirlitsstofnanna gríðarleg. Þaðþarf hins vegar ekki að fara marga tugi ára aftur til baka til þess að sjá að þessar stofnanir,sem almenningur bæði borgar fyrir og leggur traust sitt til, hafa í mörgum tilfellum viðhaldiðumdeildum efnum í umferð í tugi ára þrátt fyrir þekkt og mæld skaðleg áhrif þeirra,sérstaklega ef þau „seljast vel“. Það er aldrei fyrr en að nægilegur þrýstingur myndast ísamfélaginu sem eitthvað er tekið af markaði, en í þessu samhengi má benda á þástaðreynd að Aspartam hefur verið bannað af FDA tvisvar áður.

Hins vegar vil ég meina að á meðan að það virðist samfélagslega viðurkennt að gagnrýnastærstu ríkisstjórnir heims og opinberar stofnanir fyrir tengsl þeirra við hergagnaiðnaðinn,orkuiðnaðinn, lyfjaiðnaðinn, tóbaksiðnaðinn og fjármálaiðnaðinn að þá mætti ætla að það sé ílagi að taka matvælaiðnaðinn, líftækniiðnaðinn og efnaiðnaðinn inn í þessa formúlu líka,sérstaklega í ljósi þess að örfáum fyrirtækjum hefur tekist að rótfesta sig kyrfilega ogeinblína á að einoka megnið af matvælaframleiðslu heimsin, lobbía inn á þing og veitafjárveitingar ítrekað fyrir hagsmunum sínum inn á þing og vaða þau þannig yfir lýðræðislegtferli, neytendaréttindi almennings og löggjafarvald á skítugum skónum. Hversu skítug þurfafótspor alþjóðlegra fyrirtækjasamsteypa að vera til þess að sjá að þetta korporótískafyrirkomuleg sem við höfum búið til og aðlagast síðustu áratugi er ekki alveg að ganga upp tilframbúðar? Það er blöskrandi tilhugsun að hugsa til komandi kynslóða ef yfirgangur

einokraðra fyrirtækjasamsteypa fær að þrífast áfram í sömu mynd og birtist okkur í dag.

Öll efni hafa eiturhrifandi verkanir á einhverjum þröskuldi, meira að segja vatn og súrefni. Hérætla ég að setja mig í sömu stellingar og opinberar stofnanir með því að handveljarannsóknir sem „henta“ þeirri kenningu að Aspartam sé ekki jafn skaðlaust og EFSA o g aðrarmatvælaöryggisstofnanir, sem apa allar eftir hvor annarri án sjálfstæðra rannsókna, viljameina. Í mörgum þeirra rannsókna sem ég handvaldi er vissulega oft gefnir stærri skammtaren ráðlagður dagskammtur er samkvæmt EFSA (40mg/kg/perday), en þrátt fyrir það ernokkuð ljóst að ekki er einhuga samþykki vísindamanna um öryggi sætuefnisins. Það er ansi

magnað hversu margar óháðar rannsóknir finna vandamál við aspartam á meðan rannsóknirháðar framleiðendum finna aldrei vandamál við söluvörurnar sínar, nánast

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undantekningarlaust. Áður en flæðið byrjar er vert að nefna að frá árunum 1970-1998 vorubirtar samtalst 166 rannsóknir sem fjalla um öryggi Aspartams og af þeim voru 74fjármagnaðar af framleiðandanum sjálfum og hinar 92 fjármagnaðar af óháðum aðilum.Niðurstöður iðnaðarrannsóknanna sögðu allar (100%) til um öryggi Aspartams á meðannánast allar (92%) óháðu rannsóknirnar gerðu vart við einhverskonar vandamál.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC548217/ -

BMJ. 2005 February 5; 330(7486): 309 –310.

Independently funded studies have found potential for adverse effects

John Briffa, general practitioner

 Author information ► Copyright and License information ► 

EDITOR —Lean and Hankey's editorial on the effects of aspartame and health gives this

artificial sweetener a clean bill of health.1 However, it seems they have ignored or dismissed a

 wealth of evidence, which shows that aspartame can provoke a wide range of symptoms

including depression2and headaches.3,4 Other studies (a total of 91) that attest to aspartame's

potential for harm can be found in an online review of peer reviewed literature.5 

This review is particularly worrying as it shows that, although 100% of industry funded

(either whole or in part) studies conclude that aspartame is safe, 92% of independently

funded studies have found that aspartame has the potential for adverse effects.effects. 

 Also, while Lean and Hankey speculate on the potential of aspartame to bring about weight

loss, their assessment is largely theoretical (based on the potential for the replacement of

sugar with aspartame to bring about caloric deficit). Despite two decades of use in the human

diet, not one single, double blind, placebo controlled study that supports aspartame's

supposed weight loss effects has been published.

Lean and Hankey endorse the use of aspartame in the diet, but the facts are that this

synthetic chemical's “benefits” are unproved, and a considerable body of evidence exists that

shows it has very real potential for harm. The glaring disparity in results from industry

funded and independently funded research is clearly of considerable concern. Lean and

Hankey say that the public needs protection from “misleading” websites warning of the

hazards of aspartame. It seems that what the members of the public (and the medical

profession) really need protecting from is editorials lacking in balance and objectivity.

http://www.mpwhi.com/aspartame_methanol_and_public_health.pdf#sthash.qaPMA9mB.dpuf  - ASPARTAME: METHANOL AND THE PUBLIC HEALTH 

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Woodrow C. Monte, Ph.D., R.D.

Director of the Food Science and Nutrition Laboratory

 Arizona State University. Tempe, Arizona 85287

Published in Journal of Applied Nutrition, Volume 36, Number 1, 1984

Abstract: Aspartame (L-asparty-L-phenylalanine methyl ester), a new sweetener marketedunder the trade name NutraSweet*, releases into the human bloodstream one molecule ofmethanol for each molecule of aspartame consumed.

This new methanol source is being added to foods that have considerably reduce caloriccontent and,thus, may be consumed in large amounts. Generally, none of these foods couldbe considered dietary methanol sources prior to addition of aspartame. When diet sodas andsoft drinks, sweetened with aspartame, are used to replace fluid loss during exercise and

physical exertion in hot climates, the intake of methanol can exceed 250 mg/day or 32 timesthe Environmental Protection Agency's recommended limit of consumption for thiscumulative toxin. There is extreme variation in the human response to acute methanolpoisoning, the lowest recorded lethal oral dose being 100 mg/kg with one individual survivinga dose over ninety times this level .

Humans, due perhaps to the loss of two enzymes during evolution, are more sensitive tomethanol than any laboratory animal; even the monkey is not generally accepted as asuitable animal model. There are no human or mammalian studies to evaluate the possiblemutagenic, teratogenic, or carcinogenic effects of chronic administration of methyl alcohol s .

The average intake of methanol from natural sources varies but limited data suggests anaverage intake of considerably less than 10 mg/day . Alcoholics may average much more,with a potential range of between 0 and 600 mg/day, depending on the source and in somecases the quality of their beverages .

Ethanol, the classic antidote for methanol toxicity, is found in natural food sources ofmethanol atconcentrations 5 to 500,000 times that of the toxin (Table 1). Ethanol inhibitsmetabolism of methanoland allows the body time for clearance of the toxin through the lungsand kidneys .

The question asked whether uncontrolled consumption of this new sweetener might increase

the methanol intake of certain individuals to a point beyond which our limited knowledge of

acute and chronic human methanol toxicity can be extrapolated to predict safety.

http://www.ncbi.nlm.nih.gov/pubmed/22385158#sthash.qaPMA9mB.dpuf  - Drug Chem

Toxicol. 2013 Apr;36(2):135-40. doi: 10.3109/01480545.2012.658403. Epub 2012 Mar 2.

Long-term consumption of aspartame and brain antioxidant

defense status. Abhilash M, Sauganth Paul MV, Varghese MV, Nair RH. 

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 Source : School of Biosciences, Mahatma Gandhi University , Kottayam , India.

Abstract: The present study investigated the effect of long-term intake of aspartame, awidely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistarrats weighing 150-175 g were randomly divided into three groups as follows: The first groupwas given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group wasgiven aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL ofwater; and the control rats received 3 mL of distilled water. Oral intubations were done in themorning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activityof glutathione reductase (GR) were significantly reduced in the brain of rats that had receivedthe dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSHconcentration was observed in the 500-mg/kg b.w. aspartame-treated group.Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w.group of aspartame-treated rats. The results of this experiment indicate that long-termconsumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in thebrain, mainly through the mechanism involving the glutathione-dependent system.

http://www.ncbi.nlm.nih.gov/pubmed/16507461 - Environ Health Perspect. 2006 Mar;114(3):379-

85.

First experimental demonstration of the multipotentialcarcinogenic effects of aspartame administered in the feed toSprague-Dawley rats.

Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A. 

Source

Cesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology andEnvironmental Sciences, Bologna, Italy

Abstract: The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation hasconducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener. APM wasadministered with feed to 8-week-old Sprague-Dawley rats (100-150/sex/group), at concentrations of100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. The treatment lasted until natural death, at whichtime all deceased animals underwent complete necropsy. Histopathologic evaluation of all pathologiclesions and of all organs and tissues collected was routinely performed on each animal of all

experimental groups. The results of the study show for the first time that APM, in our experimentalconditions, causes a) an increased incidence of malignant-tumor-bearing animals with a positivesignificant trend in males (p < or = 0.05) and in females (p < or = 0.01), in particular those femalestreated at 50,000 ppm (p < or = 0.01); b) an increase in lymphomas and leukemias with a positivesignificant trend in both males (p < or = 0.05) and females (p < or = 0.01), in particular in femalestreated at doses of 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p < or = 0.05), 2,000 (p <or = 0.05), or 400 ppm (p < or = 0.01); c) a statistically significant increased incidence, with a positivesignificant trend (p < or = 0.01), of transitional cell carcinomas of the renal pelvis and ureter and theirprecursors (dysplasias) in females treated at 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p< or = 0.01), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.05); and d) an increased incidence ofmalignant schwannomas of peripheral nerves with a positive trend (p < or = 0.05) in males. The results

of this mega-experiment indicate that APM is a multipotential carcinogenic agent, even at a daily doseof 20 mg/kg body weight, much less than the current acceptable daily intake. On the basis of these

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results, a reevaluation of the present guidelines on the use and consumption of APM is urgent andcannot be delayed.

http://www.ncbi.nlm.nih.gov/pubmed/23097267 -  Am J Clin Nutr. 2012 Dec;96(6):1419-28. doi:

10.3945/ajcn.111.030833. Epub 2012 Oct 24.

Consumption of artificial sweetener- and sugar-containingsoda and risk of lymphoma and leukemia in men and women.

Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. 

Source

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital andHarvard Medical School, Boston, MA, USA. eva.schernhammer@channing.harvard.edu 

 Abstract  :BACKGROUND:

Despite safety reports of the artificial sweetener aspartame, health-related concerns remain.

OBJECTIVE:

We prospectively evaluated whether the consumption of aspartame- and sugar-containing soda is

associated with risk of hematopoetic cancers.

DESIGN:

We repeatedly assessed diet in the Nurses' Health Study (NHS) and Health Professionals Follow-Up

Study (HPFS). Over 22 y, we identified 1324 non-Hodgkin lymphomas (NHLs), 285 multiple

myelomas, and 339 leukemias. We calculated incidence RRs and 95% CIs by using Cox proportional

hazards models.

RESULTS:

When the 2 cohorts were combined, there was no significant association between soda intake and

risks of NHL and multiple myeloma. However, in men, ≥1 daily serving of diet soda increased r isks of

NHL (RR: 1.31; 95% CI: 1.01, 1.72) and multiple myeloma (RR: 2.02; 95% CI: 1.20, 3.40) in

comparison with men who did not consume diet soda. We observed no increased risks of NHL and

multiple myeloma in women. We also observed an unexpected elevated risk of NHL (RR: 1.66; 95%

CI: 1.10, 2.51) with a higher consumption of regular, sugar-sweetened soda in men but not in women.

In contrast, when sexes were analyzed separately with limited power, neither regular nor diet soda

increased risk of leukemia but were associated with increased leukemia risk when data for men and

women were combined (RR for consumption of ≥1 serving of diet soda/d when the 2 cohorts werepooled: 1.42; 95% CI: 1.00, 2.02).

CONCLUSION:

 Although our findings preserve the possibility of a detrimental effect of a constituent of diet soda, such

as aspartame, on select cancers, the inconsistent sex effects and occurrence of an apparent cancer

risk in individuals who consume regular soda do not permit the ruling out of chance as an explanation.

http://www.ncbi.nlm.nih.gov/pubmed/17805418 - Environ Health Perspect. 2007 Sep;115(9):1293-

7.

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Life-span exposure to low doses of aspartame beginningduring prenatal life increases cancer effects in rats.

Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. 

SourceCesare Maltoni Cancer Research Center, European Ramazzini Foundation of Oncology andEnvironmental Sciences, Bologna, Italy

AbstractBACKGROUND:

In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European

Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a

multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley

rats from 8 weeks of age throughout the life span.

OBJECTIVE:

The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment

during fetal life.

METHODS:

We studied groups of 70-95 male and female Sprague-Dawley rats administered APM (2,000, 400, or

0 ppm) with feed from the 12th day of fetal life until natural death.

RESULTS:

Our results show a) a significant dose-related increase of malignant tumor-bearing animals in males (p

< 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in

incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-

related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in

females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05).

CONCLUSIONS:

The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration

of APM's multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans.

Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its

carcinogenic effects are increased.

http://www.ias.ac.in/jbiosci/sep2012/679.pdf  - Effect of chronic exposure to aspartame onoxidative stress in the brain of albino mice

ASHOK IYYASWAMY and SHEELADEVI RATHINASAMY*

Department of Physiology, Dr. ALM PG Institute of Basic Medical Sciences,

University of Madras, Sekkizhar campus, Taramani, Chennai 600 113, India

Abstract: This study was aimed at investigating the chronic effect of the artificial sweeteneraspartame on oxidative stress inbrain regions of Wistar strain albino rats. Many controversial

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reports are available on the use of aspartame as itreleases methanol as one of its metabolite

during metabolism. The present study proposed to investigate whetherchronic aspartame (75

mg/kg) administration could release methanol and induce oxidative stress in the rat brain.

Tomimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to

study the aspartameeffects. Wistar strain male albino rats were administered with aspartame

orally and studied along with controls and MTX-treated controls. The blood methanol levelwas estimated, the animal was sacrificed and the free radical changes were observed in brain

discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation

(LPO) and protein thiol levels. It was observed that there was a significant increase in LPO

levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant

decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were

region specific. Chronic exposure of aspartame resulted in detectable methanol in blood.

http://www.ncbi.nlm.nih.gov/pubmed/23553132 - Folia Neuropathol. 2013;51(1):10-7.

Effects of aspartame metabolites on astrocytes and neurons.

Rycerz K, Jaworska-Adamu JE. 

Source

Department of Animal Anatomy and Histology, Faculty of Veterinary Medicine, University of LifeSciences, Lublin, Poland

Abstract Aspartame, a widespread sweetener used in many food products, is considered as a highly hazardous

compound. Aspartame was discovered in 1965 and raises a lot of controversy up to date. Astrocytesare glial cells, the presence and functions of which are closely connected with the central nervous

system (CNS). The aim of this article is to demonstrate the direct and indirect role of astrocytes

participating in the harmful effects of aspartame metabolites on neurons. The artificial sweetener is

broken down into phenylalanine (50%), aspartic acid (40%) and methanol (10%) during metabolism in

the body. The excess of phenylalanine blocks the transport of important amino acids to the brain

contributing to reduced levels of dopamine and serotonin. Astrocytes directly affect the transport of this

amino acid and also indirectly by modulation of carriers in the endothelium. Aspartic acid at high

concentrations is a toxin that causes hyperexcitability of neurons and is also a precursor of other

excitatory amino acid - glutamates. Their excess in quantity and lack of astrocytic uptake induces

excitotoxicity and leads to the degeneration of astrocytes and neurons. The methanol metabolitescause CNS depression, vision disorders and other symptoms leading ultimately to metabolic acidosis

and coma. Astrocytes do not play a significant role in methanol poisoning due to a permanent

consumption of large amounts of aspartame. Despite intense speculations about the carcinogenicity of

aspartame, the latest studies show that its metabolite - diketopiperazine - is cancirogenic in the CNS.

It contributes to the formation of tumors in the CNS such as gliomas, medulloblastomas and

meningiomas. Glial cells are the main source of tumors, which can be caused inter alia by the

sweetener in the brain. On the one hand the action of astrocytes during aspartame poisoning may be

advantageous for neuro-protection while on the other it may intensify the destruction of neurons. The

role of the glia in the pathogenesis of many CNS diseases is crucial.

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http://www.nutritionandmetabolism.com/content/10/1/44 - Prediabetic changes

in gene expression induced by aspartame and monosodium

glutamate in Trans  fat-fed C57Bl/6 J mice

Kate S Collison1*, Nadine J Makhoul1, Marya Z Zaidi1, Angela Inglis1, Bernard L

Andres1, Rosario Ubungen1, Soad Saleh1 and Futwan A Al-Mohanna12 

*Corresponding author: Kate S Collison kate@kfshrc.edu.sa 

 Author Affiliations 1Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital &

Research Centre, PO BOX 3354, Riyadh 11211, Saudi Arabia2 College of Medicin e, Al-Faisal University , Riyadh, Saudi Arabi a

Abstract : BackgroundThe human diet has altered markedly during the past four decades, with the introduction

of Transhydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase

in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and

aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. Nutrigenomics

studies in small-animal models are an established platform for analyzing the interactions between

various macro- and micronutrients. We therefore investigated the effects of changes in hepatic and

adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both

additives in C57Bl/6 J mice fed a Trans fat-enriched diet.

MethodsHepatic and adipose tissue gene expression profiles, together with body characteristics, glucose

parameters, serum hormone and lipid profiles were examined in C57Bl/6 J mice consuming one of the

following four dietary regimens, commencing in utero via the mother’s diet: [A] Trans fat (TFA) diet; [B]

MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet.

ResultsWhilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice,

the combination of ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum

free fatty acids, fasting blood glucose, HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of

significant differentially expressed genes (DEGs) showed a reduction in hepatic and adipose tissue

PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks including

PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by

ASP + MSG in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated.

Conclusion

The combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic andadipose tissue gene expression in TFA-fed C57Bl/6 J mice.

http://www.sciencedirect.com/science/article/pii/S0278691511000639 - Effect of long term intake of

aspartame on antioxidant defense status in liver

M. Abhilash, M.V. Sauganth Paul, Mathews V. Varghese, R. Harikumaran Nair  ,

School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala 686560, India

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 Abstract

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on

liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats,

weighing 150 – 175 g, were randomly divided into three groups as follows: first group was givenaspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of

1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame

(1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of

alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ

-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of

glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of

rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in both

the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-

treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term

consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status

mainly through glutathione dependent system.

http://www.ncbi.nlm.nih.gov/pubmed/7936222 - Neurology. 1994 Oct;44(10):1787-93.

Aspartame ingestion and headaches: a randomized crossover

trial.Van den Eeden SK, Koepsell TD, Longstreth WT Jr , van Belle G, Daling JR, McKnight B. 

Source

Department of Epidemiology, School of Public Health and Community Medicine, University ofWashington, Seattle 98195.

AbstractTo examine whether ingestion of aspartame is associated with headaches, we conducted a double-

blind crossover study using volunteers with self-identified headaches after using aspartame. Of the 32

subjects randomized to receive aspartame (approximately 30 mg/kg/d) and placebo in a two-treatment, four-period crossover design, 18 completed the full protocol, seven completed part of the

protocol before withdrawing due to adverse effects, three withdrew for other reasons, two were lost to

follow-up, one was withdrawn due to noncompliance, and one withdrew and gave no reason. Each

experimental period was 7 days long. Subjects reported headaches on 33% of the days during

aspartame treatment, compared with 24% on placebo treatment (p = 0.04). Subjects who were "very

sure" prior to the study that aspartame triggered some of their headaches reported larger treatment

differences (aspartame = 0.37 headache-days, placebo = 0.18 headache-days; p < 0.001) than

subjects who were "somewhat sure" (aspartame = 0.29 headache-days, placebo = 0.22 headache-

days; p = 0.51) or "not sure" (aspartame = 0.33 headache-days, placebo = 0.39 headache-days; p =

0.51). There was no significant treatment difference in the length or intensity of headaches or in the

occurrence of side effects associated with the headaches. This experiment provides evidence that,among individuals with self-reported headaches after ingestion of aspartame, a subset of this group

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report more headaches when tested under controlled conditions. It appears that some people are

particularly susceptible to headaches caused by aspartame and may want to limit their consumption.

http://www.ncbi.nlm.nih.gov/pubmed/8373935 - Biol Psychiatry. 1993 Jul 1-15;34(1-2):13-7.

Adverse reactions to aspartame: double-blind challenge inpatients from a vulnerable population.

Walton RG, Hudak R, Green-Waite RJ. 

Department of Psychiatry, Northeastern Ohio Universities College of Medicine, Youngstown.

Abstract

This study was designed to ascertain whether individuals with mood disorders are particularly

vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40

patients with unipolar depression and a similar number of individuals without a psychiatric history, the

project was halted by the Institutional Review Board after a total of 13 individuals had completed the

study because of the severity of reactions within the group of patients with a history of depression. In a

crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small

n, there was a significant difference between aspartame and placebo in number and severity of

symptoms for patients with a history of depression, whereas for individuals without such a history there

was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial

sweetener and its use in this population should be discouraged.

http://www.ncbi.nlm.nih.gov/pubmed/22025850 - J Pharmacol Pharmacother. 2011 Oct;2(4):236-43. doi: 10.4103/0976-500X.85936.

Sugar substitutes: Health controversy over perceived benefits.

Tandel KR. 

Source

Department of Pharmacology, Government Medical College, Surat, Gujarat,, India.

Abstract

Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth andwaistline. There have been some controversial suggestions that excessive sugar may play an

important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened

products continue to attract consumers. A sugar substitute (artificial sweetener) is a food additive that

duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, animal

studies have convincingly proven that artificial sweeteners cause weight gain, brain tumors, bladder

cancer and many other health hazards. Some kind of health related side effects including

carcinogenicity are also noted in humans. A large number of studies have been carried out on these

substances with conclusions ranging from "safe under all conditions" to "unsafe at any dose".

Scientists are divided in their views on the issue of artificial sweetener safety. In scientific as well as in

lay publications, supporting studies are often widely referenced while the opposing results are de-

emphasized or dismissed. So this review aims to explore the health controversy over perceivedbenefits of sugar substitutes.

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http://www.ncbi.nlm.nih.gov/pubmed/23850261 - Trends Endocrinol Metab. 2013 Sep;24(9):431-41.

doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.

Artificial sweeteners produce the counterintuitive effect of

inducing metabolic derangements.Swithers SE. 

Source

Department of Psychological Sciences and Ingestive Behavior Research Center, Purdue University,703 Third Street, West Lafayette, IN 47907, USA. swithers@purdue.edu

Abstract

The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes

has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners

like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences.

However, accumulating evidence suggests that frequent consumers of these sugar substitutes mayalso be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and

cardiovascular disease. This paper discusses these findings and considers the hypothesis that

consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned

responses that normally contribute to glucose and energy homeostasis. Because of this interference,

frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing

metabolic derangements.

http://www.ncbi.nlm.nih.gov/pubmed/23845273 - Nutrition. 2013 Nov-Dec;29(11-12):1293-9. doi:

10.1016/j.nut.2013.03.024. Epub 2013 Jul 8.

Non-nutritive sweeteners: review and update.

Shankar P,  Ahuja S, Sriram K. 

Source

Department of Health and Kinesiology, Georgia Southern University, Statesboro, GA, USA. Electronicaddress: pshankar@georgiasouthern.edu.

Abstract

Obesity has become an epidemic, not just in the United States, but also across the globe. Obesity is a

result of many factors including poor dietary habits, inadequate physical activity, hormonal issues, andsedentary lifestyle, as well as many psychological issues. Direct and indirect costs associated with

obesity-related morbidity and mortality have been estimated to be in the billions of dollars. Of the many

avenues for treatment, dietary interventions are the most common. Numerous diets have been

popularized in the media, with most being fads having little to no scientific evidence to validate their

effectiveness. Amidst this rise of weight loss diets, there has been a surge of individual products

advertised as assuring quick weight loss; one such product group is non-nutritive sweeteners (NNS).

Sugar, a common component of our diet, is also a major contributing factor to a number of health

problems, including obesity and increased dental diseases both in adults and children. Most foods

marketed towards children are sugar-laden. Obesity-related health issues, such as type 2 diabetes

mellitus, cardiovascular diseases, and hypertension, once only commonly seen in older adults, areincreasing in youth. Manufacturers of NNS are using this as an opportunity to promote their products,

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and are marketing them as safe for all ages. A systematic review of several databases and reliable

websites on the internet was conducted to identify literature related to NNS. Keywords that were used

individually or in combination included, but were not limited to, artificial sweeteners, non-nutritive

sweeteners, non-caloric sweeteners, obesity, sugar substitutes, diabetes, and cardiometabolic

indicators. The clinical and epidemiologic data available at present are insufficient to make definitive

conclusions regarding the benefits of NNS in displacing caloric sweeteners as related to energybalance, maintenance or decrease in body weight, and other cardiometabolic risk factors. Although the

FDA and most published (especially industry-funded) studies endorse the safety of these additives,

there is a lack of conclusive evidence-based research to discourage or to encourage their use on a

regular basis. While moderate use of NNS may be useful as a dietary aid for someone with diabetes or

on a weight loss regimen, for optimal health it is recommended that only minimal amounts of both

sugar and NNS be consumed.

http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022007000400004 - Int. J.

Morphol, 25(4): 689-694,2007.

Effects of Aspartame on Fetal Kidney: A Morphometric andStereological Study 

Efectos del Aspartame en el Riñon Fetal: Estudios Morfométrico yEstereológico 

Marielza R. Ismael Martins & Reinaldo Azoubel 

Post Graduate Program in Health Sciences - School of Medicine at São Jose do Rio Preto,SP, Brazil.

Dirección para correspondencia 

SUMMARY: The objective of this study was the evaluation of aspartame effects on

morphometric alterations of the glomerulus, proximal and distal convoluted tubules andcollecting ducts of the rat fetal kidney during organogénesis. Fifteen pregnant ratsaveraging 24 g body weight, were divided into 3 groups (n=5 each) of controls, ratstreated with aspartame exposed to room temperature and rats treated with aspartameheated to 40°C. Animals were given 14mg / kg aspartame by the intragastric route onthe 9th, 10th, and 11th days of pregnancy. Karyometric and stereological techniquesestimated morphological changes. A significant decrease of fetal body weight wasobserved in the group given aspartame kept at room temperature, compared to controls.Karyometry permitted the estimation of the significant nuclear variations observed in thecells of the glomerulus, proximal and distal convoluted tubules and collecting ducts ofaspartame-treated rat fetuses. Stereolgical parameters showed statistically significantlyincreased cell volume and decreased numerical cell density in fetal kidneys of rats

treated with aspartame heated to 40° compared to controls. These results indicate that

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the use of aspartame leads to alterations in all renal structures studied, suggesting thisproduct's nephrotoxicity.

http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022006000500027 - Int. J.Morphol., 24(4):679-684, 2006.

Effects of Aspartame on the Exocrine Pancreas of RatFetuses 

Efectos del Aspartame en el Páncreas Exocrino de Fetos de Ratas 

Fabíola Azevedo Genovez de Lima Leme & Reinaldo Azoubel

School of Medicine at São José do Rio Preto FAMERP, Brasil.

Correspondence to: 

SUMMARY: The present study evaluated the effects of the sweetener aspartame on thefetal pancreas, through a morphometric study, with the objective of studying the

exocrine pancreas at the end of gestational development. For this we utilized two treatedgroups, one with a solution of aspartame at ambient temperature and the other with anaspartame solution heated to 40C, and two groups treated with water ad libitum, atambient temperature and heated to 40C, respectively. On the final day of gestation thefetuses were removed and the pancreas was collected for microscopic analysis. Themorphometric study demonstrated alteration in eight out of the eleven parametersstudied in the group treated with the heated solution and one parameter altered in thegroup treated with solution at ambient temperature.

http://docsdrive.com/pdfs/ansinet/pjbs/2012/904-918.pdf  - Cytotoxic Effect of

Aspartame (Diet Sweet) on the Histological and Genetic Structures ofFemale Albino Rats and Their Offspring 

Authors: Azza A.M. Abd Elfatah --- Inas S. Ghaly --- Safaa M. Hanafy 

Journal: Pakistan Journal of Biological Sciences ISSN/EISSN: 10288880

18125735 Year: 2012 Volume: 15 Issue: 19 Pages: 904-918

Publisher: Asian Network for Scientific Information

Abstract 

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The present study evaluated the effect of aspartame intake on the

histological and genetic structures of mother albino rats and their offspring.

Sixty adult female albino rats and 180 of their offspring were equally divided

into two groups (control and treated), each group divided into three

subgroups. Each subgroup consisted of 10 pregnant rats and 30 of theiroffspring. The experimental design divided into three periods: (1) the

gestation period (subgroup one), (2) the gestation period and three weeks

after delivery (subgroup two) and (3) animals in the third subgroup treated

as subgroup two then left till the end of the ninth week after delivery. Each

pregnant rat in the treated subgroups was given a single daily dose of 1 mL

aspartame solution (50.4 mg) by gastric gavage throughout the time

intervals of experimental design. At the end of each experimental period for

control and treated subgroups, the liver of half of both control and treated

groups were subjected for histological study while the liver and bone marrow

of the other halves were subjected for cytogenetic studies. Body weight of

both groups were recorded individually twice weekly in the morning before

offering the diet. The results revealed that the rats and their offspring in the

subgroups of control animals showed increases in body weight, normal

histological sections, low chromosomal aberration and low DNA

fragmentation. The treated animals in the three subgroups rats and their

offspring revealed decreases in body weight, high histological lesions,

increases in the chromosomal aberration and DNA fragmentation comparedwith control groups. In conclusion, the consumption of aspartame leads to

histopathological lesions in the liver and alterations of the genetic system in

the liver and bone marrow of mother albino rats and their offspring. These

toxicological changes were directly proportional to the duration of its

administration and improved after its withdrawal.

http://muskingum.edu/~brianb/cv/aspartamepaper.pdf  - Aspartame decreases evoked

Neuropharmacology. 2007 Dec;53(8):967-74. Epub 2007 Sep 29.

Aspartame decreases evoked extracellular dopamine levels inthe rat brain: an in vivo voltammetry study.

Bergstrom BP, Cummings DR, Skaggs TA. 

Department of Biology, Neuroscience Program, Muskingum College, New Concord, OH 43762, USA.

brianb@muskingum.edu

Abstract

Conflicting reports exist concerning the effect aspartame (APM, l-aspartyl-l-phenylalanine methyl

ester) has upon brain biogenic amines. In the following study, in vivo voltammetry was utilized tomeasure evoked extracellular dopamine (DA) levels in the striatum of rats in order to assess APM's

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effect. Time-course experiments revealed a significant decline in evoked extracellular DA levels within

1h of a single systemic dose (500mg/kg i.p.) when compared to vehicle-injected controls. The effect

was frequency dependent and showed a significant decrease utilizing high frequency stimulation

parameters (50 and 60Hz). In order to further determine APM's potential to alter evoked extracellular

DA levels, extended stimulation periods were employed to deplete releasable stores both before and

after APM administration in intact and 6-OHDA partially lesioned animals. The extended stimulationperiods were applied at 60Hz for 2,5,10 and 20s durations. APM decreased DA levels under these

conditions in both intact and 6-OHDA partially lesioned animals by an average of 34% and 51%,

respectively. Kinetic analysis performed on frequency series indicated that the diminished DA levels

corresponded to a significant reduction in DA release. These findings suggest that APM has a

relatively potent effect of decreasing evoked extracellular DA levels when administered systemically

under the conditions specified.

http://www.sciencedirect.com/science/article/pii/S0278691511000639 - Effect of long termintake of aspartame on antioxidant defense status in liver

M. Abhilash, M.V. Sauganth Paul, Mathews V. Varghese, R. Harikumaran Nair  , School of

Biosciences, Mahatma Gandhi University, Kottayam, Kerala 686560, India 

 Abstract

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on

liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats,

weighing 150 – 175 g, were randomly divided into three groups as follows: first group was given

aspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of

1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame

(1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of

alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ

-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of

glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of

rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in boththe experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-

treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term

consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status

mainly through glutathione dependent system.

http://www.sciencedirect.com/science/article/p

ii/S0887233310002249 - 

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http://www.sciencedirect.com/science/article/pii/S0887233310002249 - n vitro effect

of aspartame in angiogenesis inductionRenata Allevaa, Battista Borghia, Lory Santarellib, Elisabetta Strafellab,Damiano Carbonarib, Massimo

Braccib, Marco Tomasettib 

a Department of Anesthesiology Research Unit, IRCCS Orthopaedic Institute Rizzoli, Bologna, Italy

b Department of Molecular Pathology and Innovative Therapies, Clinic of Occupational Medicine, Polytechnic University

of Marche, Ancona, Italyc Department of Occupational Hygiene, National Institute for Occupational Safety and

Prevention, Rome, Italy

Abstract 

 Aspartame (APM) is the most widely used artificial sweetener and is added to a wide variety of foods,

beverages, drugs, and hygiene products. In vitro  and in vivo   tests have reported contradictory data

about APM genotoxicity. We evaluated the angiogenic effect of APM in an in vitro  model using blood

vessel development assay (Angio-Kit), cultured endothelial cells and fibroblasts. The release of IL-6,

VEGF-A, and their soluble receptors sIL-R6 and sVEGFR-2 were determined over time in the

conditioned medium of the Angio-Kit system, endothelial cells and cell lines with fibroblast properties

after APM treatment. Reactive oxygen species (ROS) formation, cell viability, and stimulation of the

extracellular signal-regulated kinases (erk1/2) and protein p38 were also evaluated. Exposure to APM

induced blood vessel formation. ROS production was observed in endothelial cells after APMtreatment, which was associated with a slight cell cytotoxicity. Neither intracellular ROS formation nor

cell death was observed in fibroblasts. APM increases the levels of inflammatory mediator IL-6, VEGF

and their soluble receptors released from endothelial cells into the medium. APM treatment induces

VEGF-pathway activation by erk1/2 and p38 phosphorylation. APM at low doses is an angiogenic

agent that induces regenerative cytokine production leading to the activation of MAPKs and resulting

in the formation of new blood vessels.

http://www.sciencedirect.com/science/article/pii/S1043661805001404 - Theeffect of aspartame metabolites on human erythrocyte membrane

acetylcholinesterase activity

Stylianos Tsakirisa, ,  ,  Aglaia Giannoulia-Karantanab, Irene Simintzia, Kleopatra H. Schulpisb 

a Department of Experimental Physiology, Medical School, University of Athens, P.O. Box 65257, GR-154 01 Athens,

Greece

b Institute of Child Health, Research Center, Aghia Sophia Children's Hospital, GR-115 27 Athens, Greece

Abstract

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Studies have implicated aspartame (ASP) with neurological problems. The aim of this study was to

evaluate acetylcholinesterase (AChE) activity in human erythrocyte membranes after incubation with

the sum of ASP metabolites, phenylalanine (Phe), methanol (met) and aspartic acid (aspt), or with

each one separately. Erythrocyte membranes were obtained from 12 healthy individuals and were

incubated with ASP hydrolysis products for 1 h at 37 °C. AChE was measured spectrophotometrically.

Incubation of membranes with ASP metabolites corresponding with 34 mg/kg, 150 mg/kg or

200 mg/kg of ASP consumption resulted in an enzyme activity reduction by −33%, −41%, and −57%,

respectively. Met concentrations 0.14 mM, 0.60 mM, and 0.80 mM decreased the enzyme activity by −

20%, −32% or −40%, respectively. Aspt concentrations 2.80 mM, 7.60 mM or 10.0 mM inhibited

membrane AChE acitivity by −20%, −35%, and −47%, respectively. Phe concentrations 0.14 mM,

0.35 mM or 0.50 mM reduced the enzyme activity by −11%, −33%, and −35%, respectively. Aspt or

Phe concentrations 0.82 mM or 0.07 mM, respectively, did not alter the membrane AChE activity. It is

concluded that low concentrations of ASP metabolites had no effect on the membrane enzyme

activity, whereas high or toxic concentrations partially or remarkably decreased the membrane AChE

activity, respectively. Additionally, neurological symptoms, including learning and memory processes,

may be related to the high or toxic concentrations of the sweetener metabolites. 

http://journals.lww.com/ejhistology/pages/articleviewer.aspx?year=2013&issue=03000&article=000

18&type=abstract - The Egyptian Journal of Histology:

March 2013 - Volume 36 - Issue 1 - p 195 –205 

doi: 10.1097/01.EHX.0000425919.49371.ec

Original articles

The effect of aspartame on the pituitary thyroid axis of adult malealbino rat and the possible protective effect of Pimpinella anisumoil: histological and immunohistochemical study

El Haliem, Nesreen G.A.

Abstract

Background: Aspartame is a synthetic sweetener. Its metabolites can be toxic to many organs such asliver and kidney. Pimpinella anisum (P. anisum) has been used for different purposes as anantioxidant, hepatoprotective, and anti-inflammatory agent.

 Aim: The present work was carried out to study the histological changes in the pituitary thyroid axis ofadult male albino rats after aspartame treatment and the possible role of P. anisum in minimizingthese changes.

Materials and methods: Twenty-five adult male Albino rats were used. They were divided into threegroups: group I was the control group, group II received 250 mg/kg/day aspartame once daily for 2months, and group III received prophylactic P. anisum oil 0.5 ml/kg/day once daily, followed byaspartame after 2 h for 2 months. At the end of the experiment, the rats were sacrificed. The thyroidand pituitary gland tissue samples were processed for light microscopic and electron examination.

 Also, an immunohistochemical study was carried out for the detection of thyrotrophs.

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Results: Light microscopic examination of aspartame-treated animal showed loss of architecture of thethyroid gland. Many follicles were small in size and others had disrupted wall and detached cells intheir lumens. Some thyrocyte had pyknotic nuclei and deeply stained vacuolated cytoplasm. Therewas a highly significant increase in the number of positive immunostained thyroid-stimulating hormonecells. Most cells in pars distalis were hypertrophied with eccentric nuclei and a large negative Golgiimage. The thyrotrophs and somatotrophs had dilated cisternae of rough endoplasmic reticulum,

destroyed mitochondria, and few secretory granules. Some cells with secretory granules of bothsomatotrophs and thyrotrophs were frequently observed. The administration of P. anisum inducedimprovements in the degenerative changes of this axis.

Conclusion: From this study, it could be concluded that prolonged consumption of aspartame induceddisturbance in the pituitary thyroid axis. The use of P. anisum decreased the toxic effect of aspartame.

http://journals.lww.com/ejhistology/Abstract/2013/03000/Chronic_effect_of_aspartame_versus_ste

vioside_on.20.aspx - The Egyptian Journal of Histology:

March 2013 - Volume 36 - Issue 1 - p 213 –232 

doi: 10.1097/01.EHX.0000425981.52914.ca

Original articles

Chronic effect of aspartame versus stevioside on the cerebellarcortex of the adult albino rat: a histological andimmunohistochemical study

Mohamed, Nashwa A.

Abstract

Introduction: Sweeteners have evolved rapidly over the last 20 years and are added to a wide varietyof food items, drinks, drugs, and hygiene products. Aspartame is the most frequently used artificialsweetener. In contrast, stevioside is a sweet herb that seemed to be a promising natural candidate toreplace artificial sweeteners but was found to have hazardous effects on the male reproductivesystem.

Objectives: The aim of this work was to compare between the histological changes in the cerebellarcortex of adult rats after administration of aspartame and stevioside for 6 months. The reversibility ofthese changes was also evaluated.

Materials and methods: A total of 25 albino rats aged 3 months were used in this study. They were

divided into five groups comprising five rats each. The first group was the control group. Rats in thesecond group were given stevioside at a dose of 8.6 mg/day for 6 months. Rats in the third group weregiven stevioside for 6 months and were then allowed 1 month for recovery. Rats in the fourth groupwere given aspartame at a dose of 20 mg/day for 6 months. Rats in the fifth group were givenaspartame for 6 months and were then allowed 1 month for recovery. Specimens of the cerebellarcortex were processed for H&E and subjected to immunohistochemical staining for glial fibrillary acidicprotein (GFAP) and caspase-3 and electron microscopic study. Morphometric and statistical analyseswere performed to count the number of Purkinje cells, the number of granular cells, and the number ofGFAP and caspase-3 immunostained cells.

Results: The present study showed degenerative changes in the Purkinje and granular cell layers inboth the aspartame-treated and stevioside-treated groups. This was confirmed by a significantincrease in caspase-positive cells and a significant decrease in cell number. Moreover, there was

marked increase in the number of astrocytes in areas of degeneration. This was confirmed by asignificant increase in GFAP immunostaining. Recovery from stevioside was better than that fromaspartame, as evidenced by the normal histological appearance of Purkinje cells and less vacuolated

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neuropils. This was supported by a significant increase in the number of neurons, significant decreasein caspase-positive cells, and significant decrease in GFAP immunostaining in the recovery groupfrom stevioside compared with the recovery group from aspartame.

Conclusion: Cessation of stevioside gives better results and leads to better improvement of thehistological picture of the cerebellar cortex compared with cessation of aspartame.

http://journals.lww.com/ejhistology/Abstract/2012/12000/Histological_changes_in_adult_rat_pancr

eas_upon.24.aspx - The Egyptian Journal of Histology:

December 2012 - Volume 35 - Issue 4 - p 883 –891 

doi: 10.1097/01.EHX.0000421550.95078.47

Original articles

Histological changes in adult rat pancreas upon chronic

administration of aspartameEl-Gamal, Dalia A.; Ghafeer, Hemmat H.

Abstract

Background: Aspartame is the most popular artificial sweetener consumed by many individualsworldwide. Yet, there is still a debate on its consumption as an alternative to sugar. Further studies arewarranted to assess the effects of aspartame on pancreas morphodynamics.

 Aim of the study: The present study aimed to evaluate the effects of chronic aspartame administrationon the histological structure of rat pancreas.

Materials and methods: Twenty male albino rats aged 3 months were divided into two equal groups: acontrol group (group I) and an experimental group (group II), which included rats that received

250▒mg/kg/day aspartame once daily for 6 months. The pancreatic tails were processed for light andelectron microscopy. The pancreatic islets were evaluated by immunohistochemical stain for theidentification of insulin-secreting β cells.

Results: In group II, binucleated acinar cells, prominent nucleoli, and a relative decrease in secretorygranules were observed. Some islet cells showed an acidophilic granular cytoplasm and deeplystained nuclei. A strong positive immunoreaction for insulin was observed in β cells. Ultrastructurally,acinar cells showed euchromatic nuclei with multiple nucleoli. The proliferation and dilatation of roughendoplasmic reticulum had occurred with disturbed cell polarity. Secretory granules were deficient inmost acinar cells. β Cells showed an apparent increase in the amount of secretory granules,especially immature ones, and a variable degree of vacuolation.

Conclusion: Chronic administration of aspartame to adult rats could exert a hyperstimulatory effect onpancreatic acinar and β cells, leading to the risk of development of pancreatitis and/or diabetes. 

http://journals.lww.com/ejhistology/Abstract/2011/12000/The_effect_of_aspartame_on_the_histol

ogical.10.aspx - The Egyptian Journal of Histology:

December 2011 - Volume 34 - Issue 4 - p 715 –726 

doi: 10.1097/01.EHX.0000406589.05585.8d

Original articles

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The effect of aspartame on the histological structure of the liver andrenal cortex of adult male albino rat and the possible protectiveeffect of Pimpinella anisum oil

El Haliem, Nesreen G. A.; Mohamed, Doha S.

Abstract

Background: Aspartame is a synthetic sweetener. Its metabolites can be toxic, and it is considered amultipotential carcinogenic agent. Pimpinella anisum had been used for different purposes as ananalgesic, diuretic, and anti-inflammatory agent.

 Aim of the work: The present work was carried out to study the histological changes in the liver andrenal cortex of adult albino rats after aspartame treatment, and the possible role of P. anisum inminimizing these changes.

Materials and methods: Twenty-five adult male albino rats were used. They were divided into threegroups: group I was the control group, group II received 250 mg/kg/day aspartame once daily for 2months, and group III received prophylactic P. anisum oil 0.5 ml/kg/day once daily, followed by

aspartame after 2 h for 2 months. The liver and kidney were dissected out and processed forexamination by light and electron microscopes.

Results: Aspartame treatment induced many histological changes in the liver and kidney. Thehepatocytes exhibited irregular nuclei and a vacuolated cytoplasm. Ultrastructurally, the cytoplasmcontained multiple vacuoles and few mitochondria. In the renal cortex, some glomeruli were shrunken.There was loss of brush border of tubular epithelium. Ultrastructurally, most of the proximal convolutedtubules showed heterochromatic nuclei with a dilated nuclear envelope, mitochondria with destroyedcristae, and numerous lysosomes. The combined treatment of P. anisum oil and aspartame led to amarked improvement in most of the previously mentioned changes.

Conclusion: It was concluded that consumption of aspartame-induced hepatorenal toxicity. Using anantioxidant such as P. anisum decreased the toxicity of aspartame.

http://www.sciencedirect.com/science/article/p

ii/S0278691511004054 - Aspartame fed zebrafish

exhibit acute deaths with swimming defects and saccharin

fed zebrafish have elevation of cholesteryl ester transfer

protein activity in hypercholesterolemia

Jae-Yong Kima, 1, Juyi Seoa, 1, Kyung-Hyun Choa, b, , 

a School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea

b Protein Sensor Research Institute, Yeungnam University, Gyeongsan 712-749, Republic of Korea

Abstract

 Although many artificial sweeteners (AS) have safety issues, the AS have been widely used in

industry. To determine the physiologic effect of AS in the presence of hyperlipidemia, zebrafish were

fed aspartame or saccharin with a high-cholesterol diet (HCD). After 12 days, 30% of zebrafish, which

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consumed aspartame and HCD, died with exhibiting swimming defects. The aspartame group had

65% survivability, while the control and saccharin groups had 100% survivability. Under HCD, the

saccharin-fed groups had the highest increase in the serum cholesterol level (599 mg/dL). Aspartame-

fed group showed a remarkable increase in serum glucose (up to 125 mg/dL), which was 58% greater

than the increase in the HCD alone group. The saccharin and HCD groups had the highest cholesteryl

ester transfer protein (CETP) activity (52% CE-transfer), while the HCD alone group had 42% CE-

transfer. Histologic analysis revealed that the aspartame and HCD groups showed more infiltration of

inflammatory cells in the brain and liver sections.

Conclusively, under presence of hyperlipidemia, aspartame-fed zebrafish exhibited acute swimming

defects with an increase in brain inflammation. Saccharin-fed zebrafish had an increased atherogenic

serum lipid profile with elevation of CETP activity.

http://link.springer.com/article/10.1007/s12640-011-9264-9  - Effect of Aspartame on

Oxidative Stress and Monoamine Neurotransmitter Levels in

Lipopolysaccharide-Treated Mice 

Omar M. E. Abdel-Salam, Neveen A. Salem, Jihan Seid Hussein

 Abstract

This study aimed at investigating the effect of the sweetener aspartame on oxidative stress and brain

monoamines in normal circumstances and after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS;100 μg/kg) in mice. Aspartame (0.625– 45 mg/kg) was given via subcutaneous route at the time of endotoxin

administration. Mice were euthanized 4 h later. Reduced glutathione (GSH), lipid peroxidation (thiobarbituric

acid-reactive substances; TBARS), and nitrite concentrations were measured in brain and liver. Tumor necrosis

factor-alpha (TNF-α) and glucose were determined in brain. Alanine aminotransferase (ALT), aspartate

aminotransferase (AST), and alkaline phosphatase (ALP) were measured in liver. The administration of only

aspartame (22.5 and 45 mg/kg) increased brain TBARS by 17.7 – 32.8%, decreased GSH by 25.6 – 31.6%, and

increased TNF-α by 16.7– 44%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline,

and dopamine. Aspartame did not alter liver TBARS, nitrite, GSH, AST, ALT, or ALP. The administration ofLPS increased nitrite in brain and liver by 26.8 and 37.1%, respectively; decreased GSH in brain and liver by

21.6 and 31.1%, respectively; increased brain TNF-α by 340.4%, and glucose by 39.9%, and caused marked

increase in brain monoamines. LPS increased AST, ALT, and ALP in liver tissue by 84.4, 173.7, and 258.9%,

respectively. Aspartame given to LPS-treated mice at 11.25 and 22.5 mg/kg increased brain TBARS by 15.5 – 

16.9%, nitrite by 12.6 – 20.1%, and mitigated the increase in monoamines. Aspartame did not alter liver TBARS,nitrite, GSH, ALT, AST, or ALP. Thus, the administration of aspartame alone or in the presence of mildsystemic inflammatory response increases oxidative stress and inflammation in the brain, but not in the liver.

http://link.springer.com/chapter/10.1007/978-1-4615-9821-3_9  - Effects of Aspartame

Ingestion on Large Neutral Amino Acids and Monoamine

Neurotransmitters in the Central Nervous System  John D. Fernstrom

Dietary Phenylalanine and Brain Function1988, pp 87-94 

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 Abstract

The acute ingestion of aspartame in large doses by rats leads to rapid increments in serum tyrosine and phenylalanine levels. Such increments should enhance the uptakes of these amino acids into brain and also

antagonize the entry into brain of other large neutral amino acids. This article reviews evidence that such aminoacid effects do occur in brain following aspartame ingestion by rats and then evaluates their impact on the rates

of synthesis of the monoamine neurotransmitters.

http://www.scielo.cl/pdf/ijmorphol/v25n3/art12.pdf  - Effects of Aspartame on Maternal-Fetal

and Placental Weights, Length of Umbilical Cord and Fetal Liver: A Kariometric

Experimental Study 

- Int. J. Morphol.,

25(3):549-554, 2007.

Gabriela Soares Portela; **Reinaldo Azoubel & **Fernando Batigália

Abstract: Aspartame is a synthetic sweetener consumed by more than half the adult population in 75 countries.

Their metabolites can be toxic, principally to the liver and retina, and there are few studies on the use of

aspartame in gestation. Twenty pregnant rats were weighed and allocated randomly (n=5 per group) to receive 14

mg/kg aspartame or water by oral- gastric drip. Treated T1: aspartame diluted in water at room temperature;

Treated T2: aspartame diluted in water heated to 400 C; control Cl: water at room temperature; and control C2:

water heated to 40° C. Placentas were weighed, umbilical cords measured and 1000 nuclei of fetal hepatocytes

(250 from each group) were analyzed morphometrically utilizing the technique of kariometry, with application of

the Mann-Whitney U-Test. There were reductions in mean placental and maternal-fetal weights, in umbilical-cord

length, and the majority of kariometric parameters of the hepatocytes in the group treated with aspartame dilutedin distilled water at room temperature. Reduction of placental and maternal-fetal weights occurred, shortening of

the umbilical cord, and decrease in kariometric parameters in fetal hepatocyte nuclei after administration of

aspartame diluted in distilled water at 40°C temperature. The use of aspartame during gestation can be prejudicial

to the fetus. 

http://www.ncbi.nlm.nih.gov/pubmed/17684524 - Eur J Clin Nutr. 2008 Apr;62(4):451-62. Epub

2007 Aug 8. 

Direct and indirect cellular effects of aspartame on the brain.

Humphries P, Pretorius E, Naudé H. 

Source

Department of Anatomy, University of Pretoria, Pretoria, Gauteng, South Africa.

Abstract

The use of the artificial sweetener, aspartame, has long been contemplated and studied by various

researchers, and people are concerned about its negative effects. Aspartame is composed of

phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role

in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatoryneurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed

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from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is

converted in the body to formate, which can either be excreted or can give rise to formaldehyde,

diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been

reported that consumption of aspartame could cause neurological and behavioural disturbances in

sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that

have been encountered, and these may be accredited to changes in regional brain concentrations ofcatecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was

to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that

excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders

(DSM-IV-TR 2000) and also in compromised learning and emotional functioning.

http://www.ncbi.nlm.nih.gov/pubmed/17613990 

Ultrastruct Pathol. 2007 Mar-Apr;31(2):77-83.

Ultrastructural changes to rabbit fibrin and platelets due toaspartame.

Pretorius E, Humphries P. 

Source

Department of Anatomy, Faculty of Medicine, University of Pretoria, South Africa.resia.pretorius@up.ac.za

Abstract

The coagulation process, including thrombin, fibrin, as well as platelets, plays an important role in

hemostasis, contributing to the general well-being of humans. Fibrin formation and platelet activationare delicate processes that are under the control of many small physiological events. Any one of these

many processes may be influenced or changed by external factors, including pharmaceutical or

nutritional products, e.g., the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is

known that phenylalanine is present at position P(9) and aspartate at position P(10) of the alpha-chain

of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin by the catalyst

alpha-thrombin. The authors investigate the effect of aspartame on platelet and fibrin ultrastructure, by

using the rabbit animal model and the scanning electron microscope. Animals were exposed to 34

mg/kg of aspartame 26x during a 2-month period. Aspartame-exposed fibrin networks appeared

denser, with a thick matted fine fiber network covering thick major fibers. Also, the platelet aggregates

appeared more granular than the globular control platelet aggregates. The authors conclude by

suggesting that aspartame usage may interfere with the coagulation process and might cause delayedfibrin breakup after clot formation. They suggest this, as the fibrin networks from aspartame-exposed

rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers.

 Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to

clot formation.

http://www.ncbi.nlm.nih.gov/pubmed/17673349 

Food Chem Toxicol. 2007 Dec;45(12):2397-401. Epub 2007 Jun 16.

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The effect of aspartame metabolites on the suckling rat frontalcortex acetylcholinesterase. An in vitro study.

Simintzi I, Schulpis KH,  Angelogianni P, Liapi C, Tsakiris S. 

Source

Department of Experimental Physiology, Medical School, University of Athens, P.O. Box 65257, GR15401 Athens, Greece.

Abstract

 Aspartame (ASP) consumption is suggested to be implicated with muscarinic dysfunction. The aim of

this work was to evaluate the effect of ASP and its metabolites on acetylcholinesterase (AChE) activity

in rat frontal cortex and pure enzyme. Rat frontal cortex homogenate or pure enzyme AChE (eel E.

Electricus) were incubated with ASP and each of ASP components, phenylalanine (Phe), aspartic acid

(asp), and methanol (MeOH) for 1 h at 37 degrees C. AChE was measured spectrophotometrically.

The results showed that incubation of rat tissue or pure enzyme with the sum of ASP metabolites, as

reported to be found in the CSF after 150 or 200 mg/kg ASP consumption, inhibited frontal cortex andpure AChE about -11% to -29% (p<0.001). Asp, Phe or MeOH concentrations related to their CSF

levels after ingestion of abuse or toxic ASP doses, when separately incubated with frontal cortex or

pure AChE, resulted in a significant decrease of the enzyme activities.

IN CONCLUSION:

 ASP compounds may directly and/or indirectly act on the frontal cortex AChE. High or toxic doses of

the sweetener remarkably decreased the enzyme activity. If this in vitro finding comes into human

reality, it may be suggested that cholinergic symptoms are related to the consumption of the above

 ASP doses.

http://www.nutritionandmetabolism.com/content/10/1/44 

Prediabetic changes in gene expression induced by aspartame and

monosodium glutamate in Trans  fat-fed C57Bl/6 J mice

Kate S Collison1*, Nadine J Makhoul1, Marya Z Zaidi1, Angela Inglis1, Bernard L Andres1, Rosario Ubungen1, Soad

Saleh1 and Futwan A Al-Mohanna12 

*Corresponding author: Kate S Collison kate@kfshrc.edu.sa 

1

Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh

11211, Saudi Arabia

2College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia

Abstract

Background

The human diet has altered markedly during the past four decades, with the introduction of Transhydrogenated fat, which extended

the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as

monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake.

 Nutrigenomics studies in small-animal models are an established platform for analyzing the interactions between various macro- and

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micronutrients. We therefore investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food

additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet.

Methods

Hepatic and adipose tissue gene expression profiles, together with body characteristics, glucose parameters, serum hormone and lipid

 profiles were examined in C57Bl/6 J mice consuming one of the following four dietary regimens, commencing in utero via the

mother’s diet: [A] Trans

 fat (TFA) diet; [B] MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet. Results

Whilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice, the combination of

ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum free fatty acids, fasting blood glucose,

HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of significant differentially expressed genes (DEGs) showed a

reduction in hepatic and adipose tissue PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks

including PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by ASP + MSG

in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated.

Conclusion

The combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic and adipose tissue gene

expression in TFA-fed C57Bl/6 J mice.

http://www.nutritionandmetabolism.com/content/9/1/58 - Interactive effects of neonatal

exposure to monosodium glutamate and aspartame on glucose homeostasis

Kate S Collison1*, Nadine J Makhoul1, Marya Z Zaidi1, Rana Al-Rabiah1, Angela Inglis1, Bernard L Andres1, Rosario

Ubungen1, Mohammed Shoukri2 and Futwan A Al-Mohanna13 

*Corresponding author: Kate S Collison kate@kfshrc.edu.sa 

Author Affiliations 

1Diabetes Research Unit, Department Cell Biology, King Faisal Specialist Hospital & Research Centre, PO BOX 3354, Riyadh,

11211, Saudi Arabia

2Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital & Research Centre,

Riyadh, Saudi Arabia

3College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia

Abstract

Background

Recent evidence suggests that the effects of certain food additives may be synergistic or additive. Aspartame (ASP) and

Monosodium Glutamate (MSG) are ubiquitous food additives with a common moiety: both contain acidic amino acids which can act

as neurotransmitters , interacting with NMDA receptors concentrated in areas of the Central Nervous System regulating energy

expenditure and conservation. MSG has been shown to promote a neuroendocrine dysfunction when large quantities are

administered to mammals during the neonatal period. ASP is a low-calorie dipeptide sweetener found in a wide variety of diet

 beverages and foods. However, recent reports suggest that ASP may promote weight gain and hyperglycemia in a zebrafish

nutritional model.

Methods

We investigated the effects of ASP, MSG or a combination of both on glucose and insulin homeostasis, weight change and adiposity,

in C57BL/6 J mice chronically exposed to these food additives commencing  in-utero, compared to an additive-free diet. Pearson

correlation analysis was used to investigate the associations between body characteristics and variables in glucose and insulin

homeostasis.

Results

ASP alone (50 mg/Kgbw/day) caused an increase in fasting blood glucose of 1.6 -fold, together with reduced insulin sensitivity

during an Insulin Tolerance Test (ITT) P < 0.05. Conversely MSG alone decreased blood triglyceride and total cholesterol (T-

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CHOL) levels. The combination of MSG (120 mg/Kgbw/day) and ASP elevated body weight, and caused a further increase in

fasting blood glucose of 2.3-fold compared to Controls (prediabetic levels); together with evidence of insulin resistance during the

ITT (P < 0.05). T-CHOL levels were reduced in both ASP-containing diets in both genders. Further analysis showed a strong

correlation between body weight at 6 weeks, and body weight and fasting blood glucose levels at 17 weeks, suggesting that early

 body weight may be a predictor of glucose homeostasis in later life.

Conclusions

Aspartame exposure may promote hyperglycemia and insulin intolerance. MSG may interact with aspartame to further impair

glucose homeostasis. This is the first study to ascertain the hyperglycemic effects of chronic exposure to a combination of these

commonly consumed food additives; however these observations are limited to a C57BL/6 J mouse model. Caution should be

applied in extrapolating these findings to other species.

http://m.endo.endojournals.org/content/101/2/613.short - Analysis of theDisruption in Hypothalamic-Pituitary Regulation in Rats TreatedNeonatally with Monosodium L-Glutamate (MSG): Evidence forthe Involvement of Tuberoinfundibular Cholinergic andDopaminergic Systems in Neuroendocrine RegulationAuthors 

1.  CHARLES B. NEMEROFF*, 

2.  RICHARD J. KONKOL, 3.  GARTH BISSETTE, 4.  WILLIAM YOUNGBLOOD, 

5.  JOSEPH B. MARTIN†, 6.  PAUL BRAZEAU†, 7.  MICHAEL S. RONE, 8.  ARTHUR J. PRANGE JR., 9.  GEORGE R. BREESE and10.  JOHN S. KIZER 

1.  Biological Sciences Research Center, Departments of Pharmacology, Medicine, and Psychiatry,The Neurobiology Program, University of North Carolina School of Medicine, Chapel Hill, NorthCarolina 27514

 2. † The Division of Neurology, Montreal General Hospital, McGill University, Montreal,

Quebec Canada H3G 1A4

1.  *↵Please address correspondence to: C. B. Nemeroff, Ph.D., Biological Sciences Research Center,Division of Health Affairs, University of North Carolina, Chapel Hill, North Carolina 27514.

Abstract

Adult rats which have received monosodium-L-glutamate (MSG) (4 mg/gbody weight) on alternate days for the first ten days of life acquireneurotoxic lesions of the retina and arcuate nucleus and manifest anendocrine deficiency syndrome characterized by stunted growth, obesity,hypothyroidism, hypogonadism and pituitary atrophy. In the present study,the biochemical basis for the MSG-induced endocrine dysfunction has beenexamined and the findings of note are as follows: normal serum levels ofTSH and LH despite hypothyroidism and gonadal atrophy, and significantlyreduced serum GH levels in both males and females; elevated serum PRL

8/22/2019 Fyrir þá sem hoppa hæð sína vegna nýlegs mats EFSA á Aspartam ættu kanski að taka þann faktor inn í myndin…

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levels in males, but not females; normal or augmented pituitary release ofLH and TSH to exogenous LHRH and TRH. Within the central nervoussystem: a normal diurnal rhythm of pineal N-acetyltransferase activitydespite optic atrophy; normal concentrations of LHRH, TRH andsomatostatin within the medial basal hypothalamus; normal concentrationsof norepinephrine (NE), choline acetyltransferase (CAT) and dopamine(DA) in all extrahypothalamic regions examined; normal concentrations ofserotonin (5HT) and NE, but greatly reduced concentrations of DA (40 –50%) and CAT activity (70 –75%) in the arcuate nucleus (ARC) and medianeminence (ME) of the hypothalamus. From these findings severalconclusions were drawn: 1) The MSG-induced endocrine deficiencysyndrome appears to result from the destruction of ARC-ME dopaminergicand cholinergic tuberoinfundibular systems within the hypothalamus; 2) anormal concentration of serotonergic and noradrenergic neurons within the

hypothalamus does not insure normal central neuroendocrine regulation; 3)no more than 50% of the dopaminergic terminals in the ME arise from ARCperikarya; 4) cell bodies within the ARC contribute very few, if any, nerveterminals containing releasing factors to the ME; 5) MSG destroys theprimary optic tracts while sparing the retino-hypothalamic projection; 6)LHRH, somatostatin and TRH are not contained within cholinergic nerveterminals in the ME.

http://www.sciencedaily.com/releases/2011/06/110627183944.htm