Aspartame Notes – Mere Moonshine

NOTES

ASPARTAME

Under various names, aspartame is an ingredient in tens of thousands of consumables. some researchers suggest it is "by far" the most dangerous food additive. this is a collection of notes and articles concerning aspartame (in no particular order).

Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for G.D. Searle & Company.

Schlatter synthesized aspartame as an intermediate step in generating a tetrapeptide of the hormone gastrin.

Torunn Atteraas “Teri” Garin (1947 - 2002)

Norwegian chemical engineer who helped develop aspartame sweetener as a sugar substitute while working for General Foods (1971-85), where she became a senior laboratory manager.

1975 - US FDA task force team

Prompted by issues regarding Flagyl and Aldactone, they reviewed 25 studies submitted by the manufacturer, including 11 on aspartame. The team reported "serious deficiencies in Searle's operations and practices"

1979 - CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN)

concluded, since many problems with the aspartame studies were minor and did not affect the conclusions, the studies could be used to assess aspartame's safety.

1980 - FDA convened a Public Board of Inquiry (PBOI) consisting of independent advisors

They were charged with examining the purported relationship between aspartame and brain cancer. they concluded aspartame does not cause brain damage, but recommended against approving aspartame at that time, citing unanswered questions about cancer in laboratory rats.

1983 - the FDA approved aspartame for use in carbonated beverages

and for use in other beverages, baked goods, and confections in 1993

1985 - Monsanto Company bought G.D. Searle

the aspartame business became a separate Monsanto subsidiary, the NutraSweet Company. Prior to its 1985 merger with Monsanto, Searle is a company focusing on life sciences, specifically pharmaceuticals, agriculture, and animal health. Searle is most notable for having developed the first female birth control pill and NutraSweet.

1996 - the FDA removed all restrictions from aspartame, allowing it to be used in all foods

Several European Union countries approved aspartame in the 1980s, with EU-wide approval in 1994.

GASTRIN

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

Holland Sweetener Company

A joint venture of DSM and Tosoh, the Holland Sweetener Company manufactured aspartame using the enzymatic process developed by Toyo Soda (Tosoh) and sold as the brand Sanecta. Additionally, they developed a combination aspartame-acesulfame salt under the brand name Twinsweet. They left the sweetener industry in late 2006

MERISANT

Merisant Company is an American manufacturer formed from Monsanto Company's tabletop sweetener business, which was acquired by a group of investors in 2000. It was acquired by MacAndrews & Forbes in 2014.

INGREDIENT BRANDING

Nutrasweet is credited as the first

2000 - Monsanto sold it to J.W. Childs Equity Partners II L.P

J.W. Childs Associates, L.P. is a 27-year-old investment firm based in Boston with a long history of private equity investing, that is today focused on venture capital investments in biotechnology, pharmaceuticals, and health care consumer products.

2000 - Ajinomoto acquired NutraSweet and Euro-Aspartame from Monsanto

Ajinomoto is a Japanese multinational food and biotechnology corporation which produces seasonings, interlayer insulating materials for semiconductor packages for use in personal computers, cooking oils, frozen foods, beverages, sweeteners, amino acids, and pharmaceuticals. Aji-No-Moto (味の素, "essence of taste") is the trade name for the company's original monosodium glutamate (MSG) product, the first of its kind, since 1909.

2000 - Pharmacia Corporation was created by merging Pharmacia & Upjohn (which merged earlier?) with Monsanto and its Searle unit

The merged company was based in Peapack, New Jersey

Donald Rumsfeld (1932 – 2021)

Between 1977 and 1985, Donald Rumsfeld served as CEO, and then as president, of Searle. In 1985, he engineered the acquisition of Searle by Monsanto Corporation.

EQUAL

Equal is an American brand of artificial sweetener containing aspartame, acesulfame potassium, dextrose and maltodextrin. It is marketed as a tabletop sweetener by Merisant, a global corporation which also used to own the well-known NutraSweet brand when it was a subsidiary of Monsanto and which has headquarters in Chicago, Illinois, Switzerland, Mexico, and Singapore. In French Canada, Equal is known as "Égal". In the early 1980s, Equal and its European counterpart, Canderel, were the first aspartame-based sweeteners to be sold to the public.

CANDEREL

Canderel is a brand of artificial sweetener made mainly from aspartame. Canderel is marketed by The Merisant Company...Canderel was first marketed in France in 1979. The name "Canderel" is a combination of candi (or sugar cane) and airelles - the French word for bilberries.

NUTRASWEET

The NutraSweet Company is an American nutrient company that produces and markets NutraSweet Neotame, their trademarked brand name for the high-intensity sweetener neotame (Neotame, also known by the trade name Newtame, is a non-caloric artificial sweetener and aspartame analog by NutraSweet). In July 2018 Manus Bio Inc. bought the former NutraSweet plant in Augusta, Georgia and reopened the plant to produce the next generation of natural ingredients.

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 free amino acids. While known aspects of synthesis are covered by patents, many details are proprietary.

Two approaches to synthesis are used commercially

In the chemical synthesis, the two carboxyl groups of aspartic acid are joined into an anhydride, and the amino group is protected with a formyl group as the formamide, by treatment of aspartic acid with a mixture of formic acid and acetic anhydride.[50] Phenylalanine is converted to its methyl ester and combined with the N-formyl aspartic anhydride; then the protecting group is removed from aspartic nitrogen by acid hydrolysis. The drawback of this technique is that a byproduct, the bitter-tasting β-form, is produced when the wrong carboxyl group from aspartic acid anhydride links to phenylalanine, with desired and undesired isomer forming in a 4:1 ratio.[51] A process using an enzyme from Bacillus thermoproteolyticus to catalyze the condensation of the chemically altered amino acids will produce high yields without the β-form byproduct. A variant of this method, which has not been used commercially, uses unmodified aspartic acid, but produces low yields. Methods for directly producing aspartyl-phenylalanine by enzymatic means, followed by chemical methylation, have also been tried, but not scaled for industrial production.

PERCEIVED SWEETNESS

The perceived sweetness of aspartame (and other sweet substances like acesulfame K) in humans is due to its binding of the heterodimer G protein-coupled receptor formed by the proteins TAS1R2 and TAS1R3. Aspartame is not recognized by rodents due to differences in the taste receptors.

METABOLITES

Aspartame is rapidly hydrolyzed in the small intestines. Even with ingestion of very high doses of aspartame (over 200 mg/kg), no aspartame is found in the blood due to the rapid breakdown.

METABOLITES

Upon ingestion, aspartame breaks down into residual components, including aspartic acid, phenylalanine, methanol, and further breakdown products including formaldehyde and formic acid.

METABOLITES

Human studies show that formic acid is excreted faster than it is formed after ingestion of aspartame. In some fruit juices, higher concentrations of methanol can be found than the amount produced from aspartame in beverages.

METABOLITES

Aspartame's major decomposition products are its cyclic dipeptide (in a 2,5-Diketopiperazine, or DKP, form), the non-esterified dipeptide (aspartylphenylalanine), and its constituent components, phenylalanine, aspartic acid, and methanol. At 180 °C, aspartame undergoes decomposition to form a diketopiperazine derivative.

ASPARTATE

Aspartic acid (aspartate) is one of the most common amino acids in the typical diet. As with methanol and phenylalanine, intake of aspartic acid from aspartame is less than would be expected from other dietary sources. At the 90th percentile of intake, aspartame provides only between 1% and 2% of the daily intake of aspartic acid.

ASPARTATE

There has been some speculation that aspartame, in conjunction with other amino acids like glutamate, may lead to excitotoxicity, inflicting damage on brain and nerve cells. However, clinical studies have shown no signs of neurotoxic effects, and studies of metabolism suggest it is not possible to ingest enough aspartic acid and glutamate through food and drink to levels that would be expected to be toxic.

METHANOL

The methanol produced by the metabolism of aspartame is absorbed and quickly converted into formaldehyde and then completely oxidized to formic acid.

METHANOL

The methanol from aspartame is unlikely to be a safety concern for several reasons. Fruit juices and citrus fruits contain methanol, and there are other dietary sources for methanol such as fermented beverages and the amount of methanol produced from aspartame-sweetened foods and beverages is likely to be less than that from these and other sources that are already in people's diets.

METHANOL

With regard to formaldehyde, it is rapidly converted in the body, and the amounts of formaldehyde from the metabolism of aspartame are trivial when compared to the amounts produced routinely by the human body and from other foods and drugs. At the highest expected human doses of consumption of aspartame, there are no increased blood levels of methanol or formic acid.

REACTANT: ASPARTATE

Metabolite: Phenylethylamine - 50% of reactant metabolized - halflife: "rapid"

REACTANT: ASPARTATE

METABOLITE: ASPARTIC ACID (ASPARTATE) - 40% OF REACTANT METABOLIZED - HALFLIFE: "RAPID"

REACTANT: ASPARTATE

METABOLITE: METHANOL - 10% OF REACTANT METABOLIZED - HALFLIFE: "RAPID"

REACTANT: METHANOL

METABOLITE: FORMALDEHYDE - 100% OF REACTANT METABOLIZED - HALFLIFE: 142 MINUTES - MECHANISM: Alcohol dehydrogenase

REACTANT: FORMALDEHYDE

Metabolite: FORMIC ACID - 100% of reactant metabolized - halflife: "1 MINUTE" - MECHANISM: Catalase-Peroxide System, Cytochrome P450 Mixed-Function Oxidase System, Alcohol Dehydrogenase

REACTANT: Phenylethylamine

METABOLITE: Phenylalanine - 100% OF REACTANT METABOLIZED - MECHANISM: Phenylalanine Decarboxylation

REACTANT: Phenylalanine

METABOLITE: Phenylpyruvate (PPA)

REACTANT: Phenylpyruvate

METABOLITE: Phenyllactate (PLA)

REACTANT: Phenylpyruvate

Metabolite: Phenylacetate (PAA) - MECHANISM: Decarboxylation via Ehrlich Pathway

REACTANT: Phenylalanine

METABOLITE: Acetoacetic acid - 50% OF REACTANT METABOLIZED - MECHANISM: Phenylalanine Decarboxylation

REACTANT: Phenylalanine

METABOLITE: Fumaric acid - 50% OF REACTANT METABOLIZED

REACTANT: Phenyllactate (PLA)

METABOLITE: Phenyllactic acid - MECHANISM: Lactate Dehydrogenase

REACTANT: Phenylalanine

Metabolite: TYROSINE - MECHANISM: Phenylalanine hydroxylase

BETA-ASPARTAME

Beta-aspartame differs from aspartame based upon which carboxyl group of aspartate binds to the nitrogen of phenylalanine.

TEMPERATURE & ph

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.

STABILITY

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.

MAILLARD REACTION

Descriptive analyses of solutions containing aspartame report a sweet aftertaste as well as bitter and off-flavor aftertastes. 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.

ORIGIN

The controversy over aspartame safety originated in perceived irregularities in the aspartame approval process during the 1970s and early 1980s, including allegations of a revolving door relationship between regulators and industry and claims that aspartame producer G.D. Searle had withheld and falsified safety data.

1996 - 60 MINUTES REPORT

In 1996, the controversy reached a wider audience with a 60 Minutes report[1] that discussed criticisms of the FDA approval process and concerns that aspartame could cause brain tumors in humans. The 60 Minutes special stated that "aspartame's approval was one of the most contested in FDA history."

USENET "NANCY MARKLE"

Around the same time, a Usenet post was widely circulated under the pen name "Nancy Markle", creating the basis for a misleading and unverifiable hoax chain letter that was spread through the Internet. Numerous websites have spread the email's claims, which were not supported by scientific evidence, about safety issues purportedly linked to aspartame, including Gulf War Syndrome and lupus.

SAFETY CONCERNS

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 submitted 168 studies on aspartame, including seven animal studies that were considered crucial by the FDA. 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.

UNREPORTED MEDICAL TREATMENTS AND DISCREPANCIES IN REPORTED DATA

Other criticisms presented in the 1996 60 Minutes special of the Searle studies included assertions of unreported medical treatments that may have affected the study outcomes and discrepancies in the reported data. FDA COMMISSIONER Schmidt agreed, pending an investigation into alleged improprieties in safety studies for aspartame and several drugs.

"a pattern of conduct which compromises the scientific integrity of the studies"

In December 1975, the FDA placed a stay on the aspartame approval, preventing Searle from marketing aspartame. The Searle studies were criticized by the FDA commissioner.

15 STUDIES REVIEWED BY FDA TASK FORCE AND PANEL OF ACADEMIC PATHOLOGISTS

In 1977 and 1978, an FDA task force and a panel of academic pathologists reviewed 15 aspartame studies by Searle, and concluded that, although there were major lapses in quality control, the resulting inconsistencies would not have affected the studies' conclusions.

PUBLIC BOARD OF INQUIRY DISAGREED WITH OLNEY'S BRAIN DAMAGE CLAIMS BUT CALLED FOR MORE STUDIES INTO BRAIN CANCER CONNECTION AND REVOKED ASPARTAME APPROVAL IN THE MEANTIME

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. The board decided that further study was needed on a postulated connection between aspartame and brain tumors, and revoked approval of aspartame.

SAMUEL SKINNER, WILLIAM CONLON AND THOMAS SULLIVAN

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. Mr. Skinner's successor was in place several months later, and the statute of limitations for the alleged offenses expired.

THE FIRM - THE SEARLE FIRM

in October 1977. Despite complaints and urging from DOJ in Washington, neither the interim U.S. attorney for Chicago, William Conlon, nor Skinner's successor, Thomas Sullivan, convened a grand jury. In December, 1977, Sullivan ordered the case dropped for lack of evidence. A year and a half later, Conlon also was hired by Sidley & Austin.

THE FIRM - SIDLEY & AUSTIN

Sidley Austin LLP, is an international law firm, employing approximately 2,000 lawyers in 20 offices worldwide. The firm's headquarters is at One South Dearborn in Chicago's Loop. Directly or indirectly, Sidley Austin plays a role in 40 percent of the cases the Supreme Court hears every term. Over the last 30 years, its lawyers have argued 115 high court cases. Notable people and alumni.

FDA COMMISSIONER ARTHUR HULL HAYES, A PANEL OF FDA SCIENTISTS AND A LAWYER

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 tumors, and presented arguments both for and against approval.[2]: 53 Hayes approved the use of aspartame in dry foods. Hayes further justified his approval by citing the results of a Japanese brain tumor study,[18] the results of which, the PBOI chairman later said, would have resulted in an "unqualified approval" from the PBOI panel.[19] Several objections followed, but all were denied.

Concern about conflict of interest in this case inflamed the controversy, and Senator Metzenbaum investigated in 1981 Senate Hearings

Because of the approval controversy, Senator Howard M. Metzenbaum requested an investigation by the U.S. Government Accountability Office (GAO) of aspartame's approval.

THE PUBLIC RELATIONS AGENCY - THE SEARLE PUBLIC RELATIONS AGENCY

In November 1983, about a year after approving aspartame, Hayes left the FDA and joined the public-relations firm Burson-Marsteller, Searle's public relations agency at the time, as a senior medical adviser.

In 1987, the GAO reported that protocol had been followed and provided a time-line of events in the approval process

the GAO review included a survey of scientists who had conducted safety reviews; of the 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.

IN 1989, THE U.S. 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.

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

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.

Ralph G. Walton, a psychiatrist at Northeastern Ohio Universities College of Medicine, stated in a self-published 1996 analysis of aspartame research that industry-funded studies found no safety concerns while 84 of 92 independent studies did identify safety concerns

This analysis by Walton was submitted to the television show 60 Minutes and has been extensively discussed on the Internet. An analysis of Walton's claims showed that Walton left out at least 50 peer-reviewed safety studies from his review of the literature and that most of the research he cites as non-industry funded were actually letters to the editors, case reports, review articles or book chapters rather than published studies.

In a rebuttal to Walton's statements, the Aspartame Information Service (a service provided by Ajinomoto, a primary producer and supplier of aspartame), reviewed the publications Walton cites as critical of aspartame

arguing that most of them do not involve aspartame or do not draw negative conclusions, are not peer-reviewed, are anecdotal, or are duplicates.

Elaborate health scare, involving a hoax conspiracy theory disseminated on many websites in 1999, attributes a host of deleterious medical effects to aspartame

THIS THEORY CLAIMS THAT THE FDA APPROVAL PROCESS OF ASPARTAME WAS TAINTED AND CITES AS ITS SOURCE AN EMAIL BASED UPON A SUPPOSED TALK BY A "NANCY MARKLE" (THOUGHT TO BE BETTY MARTINI, WHO FIRST CIRCULATED THE EMAIL) AT A "WORLD ENVIRONMENTAL CONFERENCE.

1987 Nutrasweet: testimony on safety concerns over adverse neurological and behavioral effects

November 3, 1987 - The Senate Labor and Human Resources Committee heard testimony on health concerns about NutraSweet, an artificial sweetener, related to the adverse neurological and behavioral effects that had been seen in some consumers of the product. (CSPAN)

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Green synthesis of gold nanoparticles using aspartame and their catalytic activity for p-nitrophenol reduction

Demonstrated a facile and environmental-friendly approach to form gold nanoparticles through the reduction of HAuCl4 by aspartame. (WU SHUFEN, ET AL. - NANOSCALE RESEARCH LETTERS, VOLUME 10, ARTICLE ID.213, 7 PP. PUB DATE: MAY 2015)

Demonstrated the reduction of p-nitrophenol to p-aminophenol by NaBH4 is catalyzed by both monometallic and bimetallic nanoparticles (NPs). Also demonstrate a method for the synthesis of bimetallic nanoparticles using poly(amido)amine dendrimers

Pozun ZD, Rodenbusch SE, Keller E, Tran K, Tang W, Stevenson KJ, Henkelman G. A Systematic Investigation of p-Nitrophenol Reduction by Bimetallic Dendrimer Encapsulated Nanoparticles. J Phys Chem C Nanomater Interfaces. 2013 Apr 18;117(15):7598-7604. doi: 10.1021/jp312588u. Epub 2013 Apr 9. PMID: 23616909; PMCID: PMC3632091.

Gold–silver core–shell nanoparticles stabilized with a common sweetener, aspartame (AuNP@Ag@Asm), combine the antimicrobial properties of silver with the photoinduced plasmon-mediated photothermal effects of gold. The particles were tested with several bacterial strains, while biocompatibility was verified with human dermal fibroblasts

J. Am. Chem. Soc. 2014, 136, 50, 17394–17397 Publication Date: December 3, 2014 https://doi.org/10.1021/ja510435u

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THIS PAGE IS A WORK IN PROGRESS

I'm also creating an Aspartame category for space and sorting purposes which will probably be my goto. It will include most if not all of these notes in addition to new ones. It will also be a work in progress.

WHAT THE FUCK IS GOING ON HERE? YOU DECIDE.

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