Reactions to Food and Drug Additives

A. Wesley Burks MD , in Middleton's Allergy: Principles and Practice , 2020

Aspartame.

Aspartame is a nonnutritive sweetener extensively used in food and beverage applications. Numerous anecdotal reports of adverse reactions to aspartame have included headaches and various neuropsychiatric symptoms, including seizures. 103 However, no clear symptom complex ever emerged from these complaints. Furthermore, careful evaluation of individuals with self-reported aspartame sensitivity through single-blind and double-blind challenges failed to identify a single aspartame reactor out of 61 individuals evaluated. 104 In a randomized DBPC crossover study, aspartame was no more likely than placebo to elicit urticaria or angioedema. 105 Similarly, no role was found for aspartame in the provocation of chronic urticaria in DBPC challenges of patients with or without histories of sensitivities to food additives. 7,101

Aspartame

R.C. Guy , in Encyclopedia of Toxicology (Third Edition), 2014

Human Toxicity: Acute

Aspartame is nontoxic when administered as an acute dose in humans. Humans were administered aspartame at dosages up to 200 mg kg −1 body weight as a single bolus dose. Blood concentrations of aspartic acid, phenylalanine, and methanol were well below any levels considered potentially harmful. The toxic effects of methanol in humans are due to accumulation of its metabolite, formate. Blood formate concentrations did not increase after this abusive bolus dose of aspartame (equal to the amount in about 28 liters of beverage with aspartame consumed at once or about 65–70 times the amount of aspartame people consume daily at the 90th percentile). Urinary excretion of formate increased significantly in samples collected 0–4 and 4–8 h after aspartame ingestion. Therefore, the rate of formate formation did not exceed the rate of formate excretion, even after this very large bolus dose (Butchko et al., 2002; Stegink and Filer, 1984; Tschanz et al., 1996).

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Artificial sweeteners

J.K. Aronson MA, DPhil, MBChB, FRCP, HonFBPhS, HonFFPM , in Meyler's Side Effects of Drugs , 2016

Aspartame

It has been suggested that aspartame may be linked to the increase in incidence of brain tumors. Brain tumor incidence increases in the USA occurred in two distinct phases, an early modest increase that may have primarily reflected improved diagnostic technology, and a later-sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s) [ 47]. Evidence potentially implicating aspartame includes an early animal study that showed an exceedingly high incidence of brain tumors in aspartame-fed rats compared with no brain tumors in concurrent controls, the finding that aspartame has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). The authors concluded that the carcinogenic potential of aspartame needs to be reassessed.

ASPARTAME

M.B.A. Glória , in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003

Background

Aspartame is an intense nutritive sweetener discovered accidentally in 1965 by the chemist James Schlatter from G.D. Searle and Co. It was introduced in 1981 and has been assigned the INS number of 951. At present, it is available under the brand names of Nutrasweet®, Equal®, and Canderel®. Aspartame is a caloric substance because it is a dipeptide that is completely digested after consumption. However, its intense sweetness allows functionality to be achieved at very low levels, providing very few calories.

Aspartame has been approved for food, beverage, pharmaceutical, and tabletop sweetener use in more than 100 countries. Currently, it is the most widely consumed high-intensity sweetener. It is used in approximately 6000 different products and consumed by hundreds of millions of people in countries around the world.

The synthesis of aspartame can be performed by chemical or chemoenzymatic methods. There are over 70 patents on the manufacturing process. It can be made from pure amino acids and is not extracted from any food, and so it is kosher. It is also parve, which means that it contains neither dairy nor meat products. Although kosher and parve, other ingredients in a product containing aspartame must be checked for their kosher status. Aspartame sold for commercial use must meet all requirements of the Food Chemical Codex.

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Practices Need Smooth Handoff to New APM Model, AAFP Says

In American Family Physician , 2021

Health IT Roundtable, White Paper Reflect AAFP Leadership

June 10, 2021 — The AAFP participated in a recent forum on health care Information technology during and beyond the pandemic, providing input for a recently issued white paper detailing the event's findings.

Among the key takeaways of that document, "Health IT Leadership Roundtable: The Power of Technology to Transform Patient Care": the need for appropriate telehealth payment, and the importance of improving interoperability between EHRs and public health databases to ensure correct immunization tracking and timely data collection.

"This is the second Health IT Leadership Roundtable that the Academy has been involved with," AAFP Vice President and Chief Medical Informatics Officer Steven Waldren, M.D., M.S., told AAFP News. "It was an opportunity to drive our advocacy goals around health IT and gather support from other stakeholder groups to amplify our message."

Waldren said these goals were most visible in two of the paper's recommendations.

The first, labeled "Maintain Regulatory Flexibility for Virtual Care," calls for permanent adoption of certain telehealth policies introduced in response to the public health emergency.

The second of the paper's recommendations most in line with AAFP policy urges the Biden administration to "structure future funding opportunities to ensure a cross-sector approach to strengthening public health and health care systems rather than a continued siloed approach to data sharing."

It adds: "Even primary care physicians, plans and other entities do not necessarily have access to timely information to help guide individuals nor to understand which individuals have received a vaccine and which have not. While the current approach may allow for more rapid and geographically disperse administration of the vaccine, it also creates a difficult process for individuals to navigate, limiting trust in the system."

The paper also advocates for federally funded and prioritized public health infrastructure modernization and increased funding to improve and expand electronic case reporting, among other suggestions.

For more, go tohttps://www.aafp.org/news/government-medicine/20210610healthit.html.

—AAFP News Staff

Artificial sweeteners

In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016

Aspartame

Aspartame is a dipeptide that is used as an artificial sweetener. It is completely hydrolysed in the gastrointestinal tract to methanol, aspartic acid, and phenylalanine [ 2].

Aspartame appears to be a safe sweetener, and despite numerous studies of its safety during the past three decades, the incidence of serious adverse effects has been difficult to determine in controlled studies. Since one of the metabolic products of aspartame is phenylalanine, excessive use of aspartame should be avoided by patients with phenylketonuria [3–5]. Toxicity of another possible metabolic product, methanol, is unlikely, even when aspartame is used in extraordinary amounts [6,7].

Aspartame has reportedly caused angioedema and urticaria [8].

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Hazards and Diseases

M. O'Mullane , ... G. Stanley , in Encyclopedia of Food Safety, 2014

Chemical Characterization

Aspartame is a methyl ester of a dipeptide consisting of two amino acids, aspartic acid, and phenylalanine ( Figure 1). In the digestive tract, aspartame is completely hydrolyzed to its constituent amino acids in addition to methanol. On this basis, there is no systemic exposure to the parent compound. Aspartic acid, phenylalanine, and methanol are all found naturally in food at levels of intake greatly overshadowing of that arising from the gastrointestinal tract hydrolysis of aspartame. For example, aspartic acid and phenylalanine derived from aspartame intake have been calculated to be approximately 2% and 3%, respectively, of the total dietary intake of these amino acids in adults and approximately 1% of the total dietary intake in children. In addition to these metabolites, aspartame may be converted to aspartylphenylalanine diketopiperazine (DKP) when food products containing aspartame are stored under conditions of high temperatures and high pH.

Figure 1. Structure of aspartame.

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Headache

Christian Wöber , Çiçek Wöber-Bingöl , in Handbook of Clinical Neurology, 2010

Aspartame

Aspartame is an artificial sweetener. Its sweetness is 150–200 times that of sucrose. Among numerous complaints which have been related to aspartame there are many neurological symptoms, in particular headache. The proportion of patients reporting headache precipitated by aspartame ranges between 4% and 12% ( Table 12.2) and seems to be similar in migraine and TTH (Scharff et al., 1995). The findings of double-blind placebo-controlled trials are controversial (Holzhammer and Wöber, 2006a). Three studies with fewer than 20 subjects each found some relation between aspartame and headache. Three other studies (with 12, 40, and 108 participants) failed to demonstrate any relation. The daily dose administered was usually 30   mg/kg body weight. In the largest study with negative results the dose was even 75   mg/kg body weight (equivalent to 10 liters of a "light" drink). A review published by the manufacturer concludes that aspartame is safe, and that there are no unresolved questions regarding its safety under conditions of intended use (Butchko et al., 2002).

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SOFT DRINKS | Chemical Composition

K. Jorge , in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003

Aspartame

Aspartame is a sweetener made from the natural amino acids l-aspartic acid and l-phenylalanine. l-Aspartic acid is tasteless, and l-phenylalanine is slightly bitter, so the taste of aspartame could never have been predicted. Aspartame was discovered by accident in the laboratories of the Searle Company in 1965 and was first approved for use in food products in Canada 15 years later. In 1983, approval was granted by the FDA, followed by many authorities in other countries. The only negative aspect of aspartame is that it can be hazardous for people who suffer from phenylketonuria, an inherited disorder that can lead to brain damage in those exposed to phenylalanine. This disease is rare, however. Since aspartame is so sweet (about 200 times sweeter than saccharin), only a small quantity is needed, and it is therefore put into the same category as energy-free sweeteners. The calorie content can be reduced by 95% compared with corresponding drinks sweetened with saccharates. During digestion, aspartame is treated as protein, and so diabetics are able to eat and drink food sweetened with aspartame. (See AMINO ACIDS | Properties and Occurrence; ASPARTAME; PROTEIN | Chemistry; PROTEIN | Food Sources; PROTEIN | Determination and Characterization; PROTEIN | Requirements; PROTEIN | Functional Properties; PROTEIN | Interactions and Reactions Involved in Food Processing; PROTEIN | Quality; PROTEIN | Digestion and Absorption of Protein and Nitrogen Balance; PROTEIN | Synthesis and Turnover; PROTEIN | Deficiency; PROTEIN | Heat Treatment for Food Proteins; PROTEIN | Sources of Food-grade Protein.)

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SWEETENERS

M.C. Yebra-Biurrun , in Encyclopedia of Analytical Science (Second Edition), 2005

Aspartame

Aspartame [ III] is made from two amino acid components, l-aspartic acid and l-phenylalanine. Although nutritive, containing 4   kcal   g−1 like any other protein substance, due to its intense sweetness, the amounts used are small enough for aspartame to be considered and classified as a nonnutritive sweetener. In the dry form, the stability of aspartame is good and little decomposition is observed if the moisture content is kept below 8%. However, in solution, and under heat, it is not stable and undergoes hydrolysis to the free dipeptide and methanol, and cyclodehydration to its diketopiperazine derivative, in both cases with loss of sweetness. People suffering from the metabolic disorder phenylkenonuria are unable to metabolize l-phenylalanine resulting from the hydrolysis of the dipeptide and are advised to avoid this sweetener. Hydrolysis of the ester functionality affords methanol but in insufficient quantities to be harmful. Aspartame is approved in more than 90 countries (the EU, the USA, Canada, South America, Australia, Japan, etc.) for use in numerous foodstuffs.

[III]

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