Aspartame

Aspartame

Aspartame (or APM) (pronounced /ˈæspərteɪm/ or /əˈspɑrteɪm/) is an artificial, non-saccharide sweetener used as a sugar substitute in some foods and beverages. In the European Union, it is codified as E951. Aspartame is a methyl ester of the aspartic acid/phenylalanine dipeptide. It was first synthesized in 1965.

The safety of aspartame has been the subject of several political and medical controversies, Congressional hearings and internet hoaxes since its initial approval for use in food products by the U.S. Food and Drug Administration (FDA) in 1974. A 2007 medical review on the subject concluded that "the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener".[3] However, because its breakdown products include phenylalanine, aspartame must be avoided by people with the genetic condition phenylketonuria (PKU).

Chemistry

Aspartame is a methyl ester of the dipeptide of the natural amino acids L-aspartic acid and L-phenylalanine. Under strongly acidic or alkaline conditions, aspartame may generate methanol by hydrolysis. Under more severe conditions, the peptide bonds are also hydrolyzed, resulting in the free amino acids.[4]

For some markets, aspartame is manufactured from phenylalanine produced by a genetically modified strain of E. coli,[5][6] a bacterium used commonly in laboratory research and biotechnology.[7]

Properties and use

Aspartame is an artificial sweetener and is approximately 200 times sweeter than sucrose, or table sugar. Due to this property, though aspartame upon metabolism produces 4 kilocalories per gram of energy, the quantity of aspartame needed to produce a sweet taste is so small that its caloric contribution is negligible.[3] The taste of aspartame and other artificial sweeteners differ from that of table sugar in the times of onset and how long the sweetness lasts, though aspartame comes closest amongst artificial sweeteners to sugar’s taste profile. The sweetness of aspartame lasts longer than sucrose, so it is often blended with other artificial sweeteners like acesulfame potassium to produce an overall taste more like sugar.[8]

Like many other peptides, aspartame may hydrolyze (break down) into its constituent amino acids under conditions of elevated temperature or high pH. This makes aspartame undesirable as a baking sweetener, and prone to degradation in products hosting a high-pH, as required for a long shelf life. The stability of aspartame under heating can be improved to some extent by encasing it in fats or in maltodextrin. The stability when dissolved in water depends markedly on pH. At room temperature, it is most stable at pH 4.3, where its half-life is nearly 300 days. At pH 7, however, its half-life is only a few days. Most soft-drinks have a pH between 3 and 5, where aspartame is reasonably stable. In products that may require a longer shelf life, such as syrups for fountain beverages, aspartame is sometimes blended with a more stable sweetener, such as saccharin.[9]

Aspartame’s major decomposition products are its cyclic dipeptide (diketopiperazine form), the de-esterified dipeptide (aspartyl-phenylalanine), and its constituent components, phenylalanine,[10] aspartic acid,[11]and methanol.[12] At 180° C, aspartame undergoes decomposition to form a diketopiperazine (DKP) derivative.[13]

In products such as powdered beverages, the amine in aspartame can undergo a Maillard reaction with the aldehyde groups present in certain aroma compounds. The ensuing loss of both flavor and sweetness can be prevented by protecting the aldehyde as an acetal.

Descriptive analyses of solutions containing aspartame report a sweet aftertaste as well as bitter and off-flavour aftertastes.[14]

Discovery and approval

Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for G.D. Searle & Company. Schlatter had synthesized aspartame in the course of producing an antiulcer drug candidate. He accidentally discovered its sweet taste when he licked his finger, which had become contaminated with aspartame.[15]

In 1975, prompted by issues regarding Flagyl and Aldactone, a U.S. FDA task force team reviewed 25 studies submitted by the manufacturer, including 11 on aspartame. The team reported “serious deficiencies in Searle’s operations and practices".[16] The FDA sought to authenticate 15 of the submitted studies against the supporting data, in 1979 the Center for Food Safety and Applied Nutrition (CFSAN) concluded that, as any problems with the aspartame studies were minor and did not affect the conclusions, the studies could be used to assess aspartame’s safety.[16]

In 1980, the FDA convened a Public Board of Inquiry (PBOI) consisting of independent advisors charged with examining the purported relationship between aspartame and brain cancer. The PBOI concluded that aspartame does not cause brain damage, but it recommended against approving aspartame at that time, citing unanswered questions about cancer in laboratory rats.[16][17]

Citing data from a Japanese study that had not been available to the members of the PBOI,[18] and after seeking advice from an expert panel that found fault with statistical analyses underlying the PBOI’s hesitation, yet argued against approval,[19] FDA commissioner Hayes approved aspartame for use in dry goods.[20] In 1983, the FDA further approved aspartame for use in carbonated beverages, and for use in other beverages, baked goods, and confections in 1993. In 1996, the FDA removed all restrictions from aspartame, allowing it to be used in all foods.

In 1984, Monsanto Company bought G.D. Searle—and the aspartame business became a separate Monsanto subsidiary, the NutraSweet Company. On May 25, 2000, Monsanto sold it to J.W. Childs Equity Partners II L.P.[21] The U.S. patent on aspartame expired in 1992. Since then, the company has competed for market share with other manufacturers, including Ajinomoto, Merisant and the Holland Sweetener Company. The latter stopped making the chemical in late 2006 because "global aspartame markets are facing structural oversupply, which has caused worldwide strong price erosion over the last five years", making the business "persistently unprofitable".[22]

Several European Union countries approved aspartame in the 1980s, with EU-wide approval in 1994. The European Commission Scientific Committee on Food reviewed subsequent safety studies and reaffirmed the approval in 2002. The European Food Safety Authority reported in 2006 that the previously established Acceptable Daily Intake was appropriate, after reviewing yet another set of studies.[23]

Metabolism and phenylketonuria

Upon ingestion, aspartame breaks down into natural residual components, including aspartic acid, phenylalanine, methanol,[24] and further breakdown products including formaldehyde[25] and formic acid, accumulation of the latter being suspected as the major cause of injury in methanol poisoning. Human studies show that formic acid is excreted faster than it is formed after ingestion of aspartate. In some fruit juices, higher concentrations of methanol can be found than the amount produced from aspartame in beverages.[11]

High levels of the naturally-occurring essential amino acid phenylalanine are a health hazard to those born with phenylketonuria (PKU), a rare inherited disease that prevents phenylalanine from being properly metabolized. Since individuals with PKU must consider aspartame as an additional source of phenylalanine, foods containing aspartame sold in the United States must state "Phenylketonurics: Contains Phenylalanine" on their product labels.[26]

In the UK, foods that contain aspartame are legally required by the country’s Food Standards Agency to list the chemical among the product’s ingredients and carry the warning "Contains a source of phenylalanine" – this is usually at the foot of the list of ingredients. Manufacturers are also required to print ‘"with sweetener(s)" on the label close to the main product name’ on foods that contain "sweeteners such as aspartame" or "with sugar and sweetener(s)" on "foods that contain both sugar and sweetener".[27]

Marketing

Equal, NutraSweet, and Canderel are ingredients of approximately 6,000 consumer foods and beverages sold worldwide, including (but not limited to) diet sodas and other soft drinks, instant breakfasts, breath mints, cereals, sugar-free chewing gum, cocoa mixes, frozen desserts, gelatin desserts, juices, laxatives, chewable vitamins supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, instant coffees, topping mixes, wine coolers and yogurt. It is provided as a table condiment in some countries. Aspartame is less suitable for baking than other sweeteners, because it breaks down when heated and loses much of its sweetness. Aspartame is also one of the main sugar substitutes used by people with diabetes.

Ajinomoto

In 2004 the market for aspartame, in which the company Ajinomoto, the world’s largest aspartame manufacturer, had a 40 percent share, was 14,000 metric tons a year, and consumption of the product was rising by 2 percent a year.[28] Ajinomoto acquired its aspartame business in 2000 from Monsanto for $67M.[29]

In 2008, Ajinomoto sued British supermarket chain Asda, part of Wal-Mart, for a malicious falsehood action concerning its aspartame product when the chemical was listed as excluded from the chain’s product line, along with other "nasties".[30] In July 2009, a British court found in favour of Asda.[31] In June 2010, an appeal court reversed the decision, allowing Ajinomoto to pursue a case against Asda to protect aspartame’s reputation.[32] Asda said that it would continue to use the term "no nasties" on its own-label products.[33]

In November 2009, Ajinomoto announced a new brand name for its aspartame sweetener — AminoSweet.[34][35]

Competition

Because sucralose, unlike aspartame, retains its sweetness after being heated, and has at least twice the shelf life of aspartame, it has become more popular as an ingredient.[36] This, along with differences in marketing and changing consumer preferences, caused aspartame to lose market share to sucralose.[37][38] In 2004, aspartame traded at about $30/kg and sucralose, which is roughly three times sweeter by weight, at around $300/kg.[39].

Safety controversy

Main article: Aspartame controversy

Aspartame has been the subject of several controversies and hoaxes since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. Critics allege that conflicts of interest marred the FDA’s approval of aspartame, question the quality of the initial research supporting its safety,[40][41][42] and postulate that numerous health risks may be associated with aspartame.

The validity of these claims has been examined and dismissed.[43][44][45] In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame.[40][46] Aspartame has been found to be safe for human consumption by more than ninety countries worldwide,[47][48] with FDA officials describing aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut".[49] The weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener.[3]

 

The artificial sweetener aspartame has been the subject of several controversies and hoaxes since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. Critics allege that conflicts of interest marred the FDA’s approval of aspartame, question the quality of the initial research supporting its safety,[1][2][3] and postulate that numerous health risks may be associated with aspartame.

The validity of these claims has been examined and dismissed.[4][5][6] In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame.[1][7] Aspartame has been found to be safe for human consumption by more than ninety countries worldwide,[8][9] with FDA officials describing aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut".[10] The weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener.[11]

History of approval and safety

The controversy over aspartame safety originated in perceived irregularities in the aspartame approval process during the 1970s and early 1980s, including allegations of conflicts of interest and claims that aspartame producer G.D. Searle had withheld safety data. In 1996, the controversy reached a wider audience with a 60 Minutes report[12] on concerns that aspartame could cause brain tumors in humans. Around the same time, an unidentified anti-aspartame activist wrote about the subject under a pen name, creating the basis for a misleading and unverifiable hoax chain letter that was spread over the Internet.[5]

Approval in the United States

Aspartame was originally approved for use in dry foods in 1974 by then FDA Commissioner Alexander Schmidt after review by the FDA’s Center for Food Safety and Applied Nutrition. Searle had submitted 168 studies[1]:20 on aspartame, including seven animal studies that were considered crucial by the FDA.[1]:21 Soon afterwards, John Olney, a professor of psychiatry and prominent critic of MSG, along with James Turner, a public-interest lawyer and author of an anti-food-additive book, filed a petition for a public hearing, citing safety concerns.[1]:38[13]:63-4 Schmidt agreed, pending an investigation into alleged improprieties in safety studies for aspartame and several drugs. The Department of Justice instituted grand jury proceedings against Searle for fraud in one of its drug studies. In December 1975, the FDA placed a stay on the aspartame approval, preventing Searle from marketing aspartame.[1]:28

In 1977 and 1978, an FDA task force and a panel of academic pathologists reviewed 15 aspartame studies by Searle, and concluded that, although minor inconsistencies were found, they would not have affected the studies’ conclusions.[1]:4 In 1980, a Public Board of Inquiry (PBOI) heard testimony from Olney and disagreed with his claims that aspartame could cause brain damage, including in the developing fetus.[1]:40-41 The board decided that further study was needed on a postulated connection between aspartame and brain tumours, and revoked approval of aspartame.[1]:47

In 1981, FDA Commissioner Arthur Hull Hayes sought advice on the issue from a panel of FDA scientists and a lawyer. The panel identified errors underlying the PBOI conclusion that aspartame might cause brain tumours, and presented arguments both for and against approval.[1]:53 Hayes approved the use of aspartame in dry foods. Hayes further justified his approval with a Japanese brain tumor study,[14] the results of which, the PBOI chairman later said, would have resulted in an "unqualified approval" from the PBOI panel.[15] Several objections followed, but all were denied.[1]:13 In November 1983, a little more than a year after approving aspartame Hayes left the FDA and joined public-relations firm Burson-Marsteller as a senior medical advisor.[7]Because Burson-Marsteller was Searle’s public relations agency at the time, this decision would later fuel conspiracy theories.[16]

Because of the approval controversy, Senator Howard M. Metzenbaum requested an investigation by the U.S. Government Accountability Office (GAO) of aspartame’s approval. In 1987, the GAO reported that protocol had been followed and provided a timeline of events in the approval process.[1]:13 At that time, of 67 scientists who responded to a questionnaire, 12 had major concerns about Aspartame’s safety, 26 were somewhat concerned but generally confident in Aspartame safety, and 29 were very confident in Aspartame safety.[1]:16,76-81

Approval outside the US

Food additive safety evaluations by many countries have led to approval of aspartame, citing the general lack of adverse effects following consumption in reasonable quantities.[17] Food safety authorities worldwide have set acceptable daily intake (ADI) values for aspartame at 40 mg/kg of body weight based on a 1980 Joint FAO/WHO Expert Committee on Food Additives recommendation.[9] JECFA re-confirmed its evaluation in a later addendum to its monograph[18]) and the same value was approved in a December 2002 evaluation of all aspartame research by the European Commission’s Scientific Committee on Food.[9] The FDA has set its ADI for aspartame at 50 mg/kg.[19]

Based on government research reviews and recommendations from advisory bodies such as those listed above, aspartame has been found to be safe for human consumption by more than ninety countries worldwide.[8][9]

Alleged conflict of interest prior to 1996

In 1976, the FDA notified then-U.S. attorney for Chicago, Sam Skinner, of the ongoing investigation of Searle, and in January 1977, formally requested that a grand jury be convened. In February, 1977, Searle’s law firm, Sidley & Austin offered Skinner a job and Skinner recused himself from the case.[20] Mr. Skinner’s successor was in place several months later, and the statute of limitations for the alleged offenses expired in October 1977. Despite complaints and urging from DOJ in Washington, neither the interim US attorney for Chicago, William Conlon, nor Skinner’s successor, Thomas Sullivan, convened a grand jury.[21] In December, 1977, Sullivan ordered the case dropped for lack of evidence, and Conlon was later hired by Searle’s law firm. Concern about conflict of interest in this case inflamed the controversy, and Senator Metzenbaum investigated in 1981 Senate Hearings.[1] In 1989, the US Senate approved the nomination of Sam Skinner to be Secretary of Transportation, noting that both Sullivan and Senator Metzenbaum had concluded that Skinner had not acted improperly.[20]

Ralph G. Walton, a psychologist at Northeastern Ohio Universities College of Medicine, claims that funding sources may have affected the conclusions of aspartame-related research. Walton alleges that researchers with ties to industry find no safety problems, while many of those without ties to aspartame find toxicities.[16][22] In a rebuttal to Walton’s statements, the ‘Aspartame Information Service’ (a service provided by Ajinomoto, a producer of aspartame and supplier to well known food and drink makers), reviews the publications Walton cites as critical of aspartame, finding that most of them do not involve aspartame or do not draw negative conclusions, are not peer-reviewed, are anecdotal, or are duplicates.[23]

Internet rumors

An elaborate hoax disseminated through the Internet attributes deleterious medical effects to aspartame. This conspiracy theory claims that the FDA approval process of aspartame was tainted[4][5][24] and cites as its source an email based upon a supposed talk by a "Nancy Markle" at a "World Environmental Conference."[4][5][25] Specifically, the hoax websites allege that aspartame is responsible for multiple sclerosis, systemic lupus, and methanol toxicity, causing "blindness, spasms, shooting pains, seizures, headaches, depression, anxiety, memory loss, birth defects" and death.[6]

The dissemination of the Nancy Markle letter was considered so notable that the Media Awareness Network featured one version of it in a tutorial on how to determine the credibility of a web page. The tutorial implied that the Markle letter was not credible and stated that it should not be used as an authoritative source of information.[6] Betty Martini, who posted similar messages to Usenet newsgroups in late 1995 and early 1996,[5] claims that an unknown person combined her original letter with other information and redistributed it as Nancy Markle.[26][27] She believes that there is a conspiracy between the FDA and the producers of aspartame. This conspiracy theory has become a canonical example discussed on several Internet conspiracy theory andurban legend websites.[5][28][29] Although most of the allegations of this theory contradict the bulk of medical evidence,[4] this misinformation has spread around the world as chain emails since mid-December 1998,[5] influencing many websites[28] as anurban legend that continues to scare consumers.[4]

Government action and voluntary withdrawals

In 1997, due to public concerns the UK government introduced a new regulation obliging food makers who use sweeteners to state clearly next to the name of their product the phrase "with sweeteners".[30]

In 2007, the Indonesian government considered banning Aspartame.[31] In the Philippines, the small political party Alliance for Rural Concerns introduced House Bill 4747 in 2008 with the aim of having aspartame banned from the food supply.[32] The US state of New Mexico introduced a bill to ban aspartame in 2007,[33][34][35] and Hawaiian legislators signed a 2009 resolution asking the FDA to rescind approval.[36] In March 2009, the California OEHHA identified aspartame as a chemical for consultation by its Carcinogen Identification Committee, in accordance with California state Proposition 65.[37]

In 2007, the UK supermarket chains Sainsbury’s,[38] M&S,[39] and Wal-Mart subsidiary Asda,[40] announced that they would no longer use aspartame in their own label products.[41] In April 2009, Ajinomoto Sweeteners Europe, the makers of Aspartame in Europe, responded to Asda’s ‘no nasties’ campaign by filing a complaint of malicious falsehood against Asda in the English courts.[42][43] In July 2009, Asda won the legal case after the trial judge construed the ‘no nasties’ labelling to "not mean that aspartame was potentially harmful or unhealthy", though it might be appealed.[44][45]

In 2009, the South African retailer Woolworths announced it was removing aspartame from its own-brand foods.[46]

In 2010, the British Food Standards Agency launched an investigation into aspartame amid claims that some people experience side-effects after consuming the substance.[47]

Consumption

A 12 ounce can of diet soda contains 180 mg of aspartame,[48] and one liter of aspartame-sweetened soda contains 600 mg aspartame.[49] U.S. diet beverage consumers average approximately 200 mg of daily aspartame consumption.[48] For a 75 kilograms (165 lb) adult, it takes approximately 21 cans of diet soda to consume the 3,750 mg of aspartame that would surpass the FDA’s 50 milligrams per kilogram of bodyweight ADI of aspartame.[48] Surveys of aspartame intake, particularly via diet soda, indicate that even consumers with high aspartame intake are typically "well below" the EFSA‘s 40 mg/kg ADI.[50][51][52] The European Commission’s Scientific Committee on Food concluded in 2002 that, while some minor effects on health may occur at very high doses, no effects are expected at normal levels of consumption.[53][54]

Safety and analysis

Large scale analyses by scientists and government bodies have concluded that aspartame is safe for dietary consumption by humans. A 2007 study, published in Annals of Oncology of the European Society for Medical Oncology, reviewed Italian studies of instances of cancer from 1991 and 2004 and concluded a "lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms".[55]

In 2006, the US National Cancer Institute concluded in a study of over 470,000 men and women aged 50 to 69 that there was no statistically significant link between aspartame consumption and leukemias, lymphomas or brain tumors.[56] The study compared how much of 4 types of aspartame-sweetened beverages the subjects said they had drunk in 1995 or 1996 to how likely they were to have developed these cancers during the following five years.[57] This conclusion was questioned in letters to the editors[58][59] which pointed out that the study did not consider non-beverage consumption of aspartame, did not estimate the subjects’ long-term use of aspartame, and did not include any subjects who had consumed aspartame since childhood (as the subjects were all over 49 and aspartame beverages had only been on the market for 15 years). The letters concluded that the study design was inappropriate to test the stated hypothesis.

In two widely criticised and later discounted studies,[11][60] the European Ramazzini Foundation of Oncology and Environmental Sciences (ERF) reported[61] what they claimed was a dose-independent, statistically significant increase in several malignancies of rats, concluding that aspartame is a potential carcinogen at normal dietary doses. After reviewing the foundation’s claims, the European Food Safety Authority (EFSA)[62] the U.S. Food and Drug Administration (FDA)[63] discounted the study results and found no reason to revise their previously established acceptable daily intake levels for aspartame. Other reported flaws included: comparing cancer rates of older aspartame-consuming rats to younger control rats; unspecified composition of the "Corticella" diet and method of adding aspartame, leading to possible nutritional deficiencies; unspecified aspartame storage conditions; lack of animal randomization; overcrowding and a high incidence of possibly carcinogenic infections; and the U.S. National Toxicology Program’s finding that the ERF had misdiagnosed hyperplasias as malignancies.[11] The U.S. FDA requested the study’s data and offered to review tissue slides, but the Ramazzini Foundation did not send all of the data and withheld its pathology slides. From the materials received, the FDA found that the data did not support the researcher’s published conclusions.[63]

Several other scientists support the most recent ERF study.[64] Two scientists referred to the newer study in their comments regarding the potential risks to workers who produce aspartame and are exposed to it under long-term conditions. They proposed that the FDA "should consider sponsoring a prospective epidemiologic study of aspartame workers."[65]

The New Zealand Food Safety Authority (NZFSA) also questioned the validity and significance of the Ramazzini studies, stating, "These studies were conducted in a way that could not possibly have provided any information about the toxicity of aspartame – or in fact anything else in the rats’ diet. … In fact, the only conclusion that can be drawn from the results is that aspartame appears to be safe because the studies showed that those rats fed it (even at very high doses) lived as long (if not longer) as untreated rats, despite consuming up to more than 100 times the ADI every day of their lives. If aspartame was as horrendously toxic as is being claimed, it would be logical to expect the rats dosed with it to have shortened life-spans. The conclusions drawn by the researchers were clearly not backed up by their own data."[66]

Scientific studies of aspartame ingestion by humans have found no adverse effects,[55][67][68][69][70][71] but several scientists have recommended further research into postulated connections between aspartame and an increase in malignant brain tumorsfrom 1982 to 1992[72] and in lymphoma.[61] Although some reports have proposed a connection between aspartame and headache or migraine in susceptible individuals,[73][74] the overall scientific evidence indicates that aspartame does not cause headaches.[75]

Hypotheses of adverse health effects have focused on three metabolites of aspartame. A review of the effects of those metabolites has established that aspartame and its metabolites are safe and that there are no adverse reactions.[62]

Methanol and formaldehyde

Approximately 10% of aspartame (by mass) is broken down into methanol in the small intestine. Most of the methanol is absorbed and quickly converted into formaldehyde and then to formic acid.[76] Some opponents of aspartame have falsely claimed that this causes metabolic acidosis.[28] The metabolism of aspartame does not damage the body because: (a) the quantity of methanol produced is too small to disrupt normal physiological processes;[75] (b) methanol and formaldehyde are natural by-products of human metabolism and are safely processed by various enzymes;[75] (c) there is more methanol in some natural fruit juices and alcoholic beverages than is derived from aspartame ingestion;[75][77] and (d) even large doses of pure methanol have been shown in non-human primate studies to lead to ample accumulation of formic acid (as formate), while no formaldehyde was detected.[78]

In experiments on rodents given radiolabeled aspartame, labeled protein and DNA accumulated in the brain, liver, kidneys and other tissues after ingestion of either 20 mg/kg or 200 mg/kg of aspartame.[76] However, these scientists were not directly measuring formaldehyde, but simply measuring levels of some by-product of the methanol from aspartame.[75]

Phenylalanine

Fifty percent of aspartame by mass is broken down into phenylalanine, one of the nine essential amino acids commonly found in foods and a precursor to tyrosine. A rise in blood plasma phenylalanine is negligible in typical use of aspartame[79] and their studies show no significant effects on neurotransmitter levels in the brain or changes in seizure thresholds.[80][81][82] Adverse effects of phenylalanine on fetuses have been observed only when blood phenylalanine levels remain at high levels as opposed to spiking occasionally.[83]

Aspartic acid

40% of aspartame by mass is broken down into aspartic acid (aspartate), an amino acid. At high concentrations, aspartate can act as an excitotoxin, inflicting damage on brain and nerve cells.[84][85]

Humans and other primates are not as susceptible to excitotoxins as rodents; therefore, it is problematic to make conclusions about human safety from high-dose excitoxin response in rodent studies.[86][87] Increases in blood plasma levels of aspartic acid after ingestion of aspartame are insufficient to cause concern for human subjects researchers.[88][89]

Aspartylphenylalanine diketopiperazine

Aspartylphenylalanine diketopiperazine, a type of diketopiperazine (DKP), is created in products as aspartame breaks down over time. For example, researchers found that 6 months after aspartame was put into carbonated beverages, 25% of the aspartame had been converted to DKP.[49]

Concern among some scientists has been expressed that this form of DKP would undergo a nitrosation process in the stomach producing a type of chemical that could cause brain tumors.[72][90] However, the nitrosation of aspartame or the DKP in the stomach likely does not produce chemicals that cause brain tumors.[75] In addition, only a minuscule amount of the nitrosated chemical can be produced.[91] There are very few human studies on the effects of this form of DKP. However, a (one-day) exposure study showed that the DKP was tolerated without adverse effects.[92]

Insulin resistance

Some aspartame critics, particularly those in weight loss communities, claim that aspartame contributes to weight gain and obesity due to purported spikes in the insulin level.[93] The argument holds that aspartame causes the body to secrete excess insulin. If true, this could lead to insulin resistance, weight gain, and possibly type II diabetes — health outcomes that consumers may be trying to prevent by using diet foods and sodas. However, recent studies have shown that aspartame does not increase glucose nor insulin blood levels and cannot be directly linked to insulin resistance or diabetes.[94]

Flight performance

A 1991 study published in the medical journal Aviation, Space, and Environmental Medicine reported that there were anecdotal concerns about aspartame and the cognitive performance of pilots; however, its double-blind study found no detectable effect of aspartame on pilot performance.[95] In 1992, the US Air Force magazine Flying Safety published an article which expressed such anecdotal concerns and warned that a few pilots who drink diet sodas containing aspartame could be more susceptible to conditions ranging from flicker vertigo to gradual loss of vision.[96]

Depression

In 1994, a double-blind study was halted by the institutional review board when eight patients with acute depression exhibited an increased expression of their symptoms after they consumed aspartame. On this basis, the authors of the study recommended that patients with unipolar depression avoid the sweetener.[97] Independent authors commenting on the study have cautioned against drawing conclusions from the uncontrolled study considering the everyday experience of depressed people exposed to aspartame. The authors also addressed issues of publication bias, "Potential for positive publication bias in studies funded by manufacturers undoubtedly exists, but this can also apply to studies designed by those seeking to prove a strong belief about hazards of food components."[98]

Aspartame2

Aspartame is, by far, the most dangerous substance on the market that is added to foods.

http://www.mercola.com/article/aspartame/dangers.htm

Aspartame is the technical name for the brand names NutraSweet, Equal, Spoonful, and Equal-Measure. It was discovered by accident in 1965 when James Schlatter, a chemist of G.D. Searle Company, was testing an anti-ulcer drug.

Aspartame was approved for dry goods in 1981 and for carbonated beverages in 1983. It was originally approved for dry goods on July 26, 1974, but objections filed by neuroscience researcher Dr John W. Olney and Consumer attorney James Turner in August 1974 as well as investigations of G.D. Searle’s research practices caused the U.S. Food and Drug Administration (FDA) to put approval of aspartame on hold (December 5, 1974). In 1985, Monsanto purchased G.D. Searle and made Searle Pharmaceuticals and The NutraSweet Company separate subsidiaries.

Aspartame accounts for over 75 percent of the adverse reactions to food additives reported to the FDA. Many of these reactions are very serious including seizures and death.(1) A few of the 90 different documented symptoms listed in the report as being caused by aspartame include: Headaches/migraines, dizziness, seizures, nausea, numbness, muscle spasms, weight gain, rashes, depression, fatigue, irritability, tachycardia, insomnia, vision problems, hearing loss, heart palpitations, breathing difficulties, anxiety attacks, slurred speech, loss of taste, tinnitus, vertigo, memory loss, and joint pain.

According to researchers and physicians studying the adverse effects of aspartame, the following chronic illnesses can be triggered or worsened by ingesting of aspartame:(2) Brain tumors, multiple sclerosis, epilepsy, chronic fatigue syndrome, parkinson’s disease, alzheimer’s, mental retardation, lymphoma, birth defects, fibromyalgia, and diabetes.

Aspartame is made up of three chemicals: aspartic acid, phenylalanine, and methanol. The book "Prescription for Nutritional Healing," by James and Phyllis Balch, lists aspartame under the category of "chemical poison." As you shall see, that is exactly what it is.

What Is Aspartame Made Of?

Aspartic Acid (40 percent of Aspartame)

Dr. Russell L. Blaylock, a professor of neurosurgery at the Medical University of Mississippi, recently published a book thoroughly detailing the damage that is caused by the ingestion of excessive aspartic acid from aspartame. Blaylock makes use of almost 500 scientific references to show how excess free excitatory amino acids such as aspartic acid and glutamic acid (about 99 percent of monosodium glutamate (MSG) is glutamic acid) in our food supply are causing serious chronic neurological disorders and a myriad of other acute symptoms.(3)

How Aspartate (and Glutamate) Cause Damage

Aspartate and glutamate act as neurotransmitters in the brain by facilitating the transmission of information from neuron to neuron. Too much aspartate or glutamate in the brain kills certain neurons by allowing the influx of too much calcium into the cells. This influx triggers excessive amounts of free radicals, which kill the cells. The neural cell damage that can be caused by excessive aspartate and glutamate is why they are referred to as "excitotoxins." They "excite" or stimulate the neural cells to death.
Aspartic acid is an amino acid. Taken in its free form (unbound to proteins) it significantly raises the blood plasma level of aspartate and glutamate. The excess aspartate and glutamate in the blood plasma shortly after ingesting aspartame or products with free glutamic acid (glutamate precursor) leads to a high level of those neurotransmitters in certain areas of the brain.

The blood brain barrier (BBB), which normally protects the brain from excess glutamate and aspartate as well as toxins, 1) is not fully developed during childhood, 2) does not fully protect all areas of the brain, 3) is damaged by numerous chronic and acute conditions, and 4) allows seepage of excess glutamate and aspartate into the brain even when intact.

The excess glutamate and aspartate slowly begin to destroy neurons. The large majority (75 percent or more) of neural cells in a particular area of the brain are killed before any clinical symptoms of a chronic illness are noticed. A few of the many chronic illnesses that have been shown to be contributed to by long-term exposure to excitatory amino acid damage include:

  • Multiple sclerosis (MS)
  • ALS
  • Memory loss
  • Hormonal problems
  • Hearing loss
  • Epilepsy
  • Alzheimer’s disease
  • Parkinson’s disease
  • Hypoglycemia
  • AIDS
  • Dementia
  • Brain lesions
  • Neuroendocrine disorders

The risk to infants, children, pregnant women, the elderly and persons with certain chronic health problems from excitotoxins are great. Even the Federation of American Societies for Experimental Biology (FASEB), which usually understates problems and mimics the FDA party-line, recently stated in a review that:

"It is prudent to avoid the use of dietary supplements of L-glutamic acid by pregnant women, infants, and children. The existence of evidence of potential endocrine responses, i.e., elevated cortisol and prolactin, and differential responses between males and females, would also suggest a neuroendocrine link and that supplemental L-glutamic acid should be avoided by women of childbearing age and individuals with affective disorders."(4)

Aspartic acid from aspartame has the same deleterious effects on the body as glutamic acid.

The exact mechanism of acute reactions to excess free glutamate and aspartate is currently being debated. As reported to the FDA, those reactions include:(5)

  • Headaches/migraines
  • Nausea
  • Abdominal pains
  • Fatigue (blocks sufficient glucose entry into brain)
  • Sleep problems
  • Vision problems
  • Anxiety attacks
  • Depression
  • Asthma/chest tigShtness.

One common complaint of persons suffering from the effect of aspartame is memory loss. Ironically, in 1987, G.D. Searle, the manufacturer of aspartame, undertook a search for a drug to combat memory loss caused by excitatory amino acid damage. Blaylock is one of many scientists and physicians who are concerned about excitatory amino acid damage caused by ingestion of aspartame and MSG.

A few of the many experts who have spoken out against the damage being caused by aspartate and glutamate include Adrienne Samuels, Ph.D., an experimental psychologist specializing in research design. Another is Olney, a professor in the department of psychiatry, School of Medicine, Washington University, a neuroscientist and researcher, and one of the world’s foremost authorities on excitotoxins. (He informed Searle in 1971 that aspartic acid caused holes in the brains of mice.)

Phenylalanine (50 percent of aspartame)

Phenylalanine is an amino acid normally found in the brain. Persons with the genetic disorder phenylketonuria (PKU) cannot metabolize phenylalanine. This leads to dangerously high levels of phenylalanine in the brain (sometimes lethal). It has been shown that ingesting aspartame, especially along with carbohydrates, can lead to excess levels of phenylalanine in the brain even in persons who do not have PKU.

This is not just a theory, as many people who have eaten large amounts of aspartame over a long period of time and do not have PKU have been shown to have excessive levels of phenylalanine in the blood. Excessive levels of phenylalanine in the brain can cause the levels of seratonin in the brain to decrease, leading to emotional disorders such as depression. It was shown in human testing that phenylalanine levels of the blood were increased significantly in human subjects who chronically used aspartame.(6)

Even a single use of aspartame raised the blood phenylalanine levels. In his testimony before the U.S. Congress, Dr. Louis J. Elsas showed that high blood phenylalanine can be concentrated in parts of the brain and is especially dangerous for infants and fetuses. He also showed that phenylalanine is metabolised much more effeciently by rodents than by humans.(7)

One account of a case of extremely high phenylalanine levels caused by aspartame was recently published the "Wednesday Journal" in an article titled "An Aspartame Nightmare." John Cook began drinking six to eight diet drinks every day. His symptoms started out as memory loss and frequent headaches. He began to crave more aspartame-sweetened drinks. His condition deteriorated so much that he experienced wide mood swings and violent rages. Even though he did not suffer from PKU, a blood test revealed a phenylalanine level of 80 mg/dl. He also showed abnormal brain function and brain damage. After he kicked his aspartame habit, his symptoms improved dramatically.(8)

As Blaylock points out in his book, early studies measuring phenylalanine buildup in the brain were flawed. Investigators who measured specific brain regions and not the average throughout the brain notice significant rises in phenylalanine levels. Specifically the hypothalamus, medulla oblongata, and corpus striatum areas of the brain had the largest increases in phenylalanine. Blaylock goes on to point out that excessive buildup of phenylalanine in the brain can cause schizophrenia or make one more susceptible to seizures.

Therefore, long-term, excessive use of aspartame may provid a boost to sales of seratonin reuptake inhibitors such as Prozac and drugs to control schizophrenia and seizures.

Methanol (aka wood alcohol/poison) (10 percent of aspartame)

Methanol/wood alcohol is a deadly poison. Some people may remember methanol as the poison that has caused some "skid row" alcoholics to end up blind or dead. Methanol is gradually released in the small intestine when the methyl group of aspartame encounter the enzyme chymotrypsin.

The absorption of methanol into the body is sped up considerably when free methanol is ingested. Free methanol is created from aspartame when it is heated to above 86 Fahrenheit (30 Centigrade). This would occur when aspartame-containing product is improperly stored or when it is heated (e.g., as part of a "food" product such as Jello).

Methanol breaks down into formic acid and formaldehyde in the body. Formaldehyde is a deadly neurotoxin. An EPA assessment of methanol states that methanol "is considered a cumulative poison due to the low rate of excretion once it is absorbed. In the body, methanol is oxidized to formaldehyde and formic acid; both of these metabolites are toxic." They recommend a limit of consumption of 7.8 mg/day. A one-liter (approx. 1 quart) aspartame-sweetened beverage contains about 56 mg of methanol. Heavy users of aspartame-containing products consume as much as 250 mg of methanol daily or 32 times the EPA limit.(9)

Symptoms from methanol poisoning include headaches, ear buzzing, dizziness, nausea, gastrointestinal disturbances, weakness, vertigo, chills, memory lapses, numbness and shooting pains in the extremities, behavioral disturbances, and neuritis. The most well known problems from methanol poisoning are vision problems including misty vision, progressive contraction of visual fields, blurring of vision, obscuration of vision, retinal damage, and blindness. Formaldehyde is a known carcinogen, causes retinal damage, interferes with DNA replication and causes birth defects.(10)

Due to the lack of a couple of key enzymes, humans are many times more sensitive to the toxic effects of methanol than animals. Therefore, tests of aspartame or methanol on animals do not accurately reflect the danger for humans. As pointed out by Dr. Woodrow C. Monte, director of the food science and nutrition laboratory at Arizona State University, "There are no human or mammalian studies to evaluate the possible mutagenic, teratogenic or carcinogenic effects of chronic administration of methyl alcohol."(11)

He was so concerned about the unresolved safety issues that he filed suit with the FDA requesting a hearing to address these issues. He asked the FDA to "slow down on this soft drink issue long enough to answer some of the important questions. It’s not fair that you are leaving the full burden of proof on the few of us who are concerned and have such limited resources. You must remember that you are the American public’s last defense. Once you allow usage (of aspartame) there is literally nothing I or my colleagues can do to reverse the course. Aspartame will then join saccharin, the sulfiting agents, and God knows how many other questionable compounds enjoined to insult the human constitution with governmental approval."(10) Shortly thereafter, the Commissioner of the FDA, Arthur Hull Hayes, Jr., approved the use of aspartame in carbonated beverages, he then left for a position with G.D. Searle’s public relations firm.(11)

It has been pointed out that some fruit juices and alcoholic beverages contain small amounts of methanol. It is important to remember, however, that methanol never appears alone. In every case, ethanol is present, usually in much higher amounts. Ethanol is an antidote for methanol toxicity in humans.(9) The troops of Desert Storm were "treated" to large amounts of aspartame-sweetened beverages, which had been heated to over 86 degrees F in the Saudi Arabian sun. Many of them returned home with numerous disorders similar to what has been seen in persons who have been chemically poisoned by formaldehyde. The free methanol in the beverages may have been a contributing factor in these illnesses. Other breakdown products of aspartame such as DKP (discussed below) may also have been a factor.

In a 1993 act that can only be described as "unconscionable," the FDA approved aspartame as an ingredient in numerous food items that would always be heated to above 86 degree F (30 degree C).

Diketopiperazine (DKP)

DKP is a byproduct of aspartame metabolism. DKP has been implicated in the occurrence of brain tumors. Olney noticed that DKP, when nitrosated in the gut, produced a compound that was similar to N-nitrosourea, a powerful brain tumor causing chemical. Some authors have said that DKP is produced after aspartame ingestion. I am not sure if that is correct. It is definitely true that DKP is formed in liquid aspartame-containing products during prolonged storage.

G.D. Searle conducted animal experiments on the safety of DKP. The FDA found numerous experimental errors occurred, including "clerical errors, mixed-up animals, animals not getting drugs they were supposed to get, pathological specimens lost because of improper handling," and many other errors.(12) These sloppy laboratory procedures may explain why both the test and control animals had sixteen times more brain tumors than would be expected in experiments of this length.

In an ironic twist, shortly after these experimental errors were discovered, the FDA used guidelines recommended by G.D. Searle to develop the industry-wide FDA standards for good laboratory practices.(11)

DKP has also been implicated as a cause of uterine polyps and changes in blood cholesterol by FDA Toxicologist Dr. Jacqueline Verrett in her testimony before the U.S. Senate.(13)

http://www.mercola.com/article/aspartame/dangers.htm

Aspartame: Sweet Misery A Poisoned World

1:29:54 – 1 year ago

This is the movie that Pepsi and Coca Cola don’t want you to see.

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