International Regulations on Amino Acid Use in Foods and Supplements and Recommendations to Control Their Safety Based on Purity and Quality

Abstract

We examined international regulatory developments related to the use of proteinogenic amino acids in human nutrition and concluded that the current risk-assessment practices tend to focus exclusively on setting maximum daily limits. In this brief review we argue that controlling the standards of purity and ingredient quality are the key safety issues that should be considered during risk assessment. Moreover, if maximum intake limits on amino acids are implemented, they should be defined using a well-established rationale for the health risks associated with high intakes. This would avoid setting limits that are so low that they render the dietary supplements ineffective and which, therefore, could mislead the consumer. We further suggest that there should be greater regional concordance in how the use of amino acids as ingredients is regulated and use the capacity of industry to oversee pre-competitive issues, such as standards of purity and scientific research on the safety of generic ingredients. Our arguments are based on clinical safety scientific research and oversights of amino acid purity standards conducted in the last decade by the not-for-profit international association, the International Council on Amino Acid Science.

Detection of impurities in dietary supplements containing l-tryptophan

“…Although the evaluated Trp-containing products represent a small segment of commercial products (NIH 2021 ) the results point towards a need to improve the enforcement of purity standards for Trp and other functional ingredients in dietary supplements (Rogers and Smriga 2012 ). Alas, many national authorities regulate ingredients in dietary supplements only by establishing maximum limits on daily intake (Smriga 2020 ). Using Trp as a typical ingredient in supplements, this is a paradoxical regulatory approach since a controlled clinical safety study in healthy adults described a substantial safety margin for high-purity supplementary Trp equal to more than 5-times its intake from regular food sources (Hiratsuka et al 2013 ).…”

“…The not-for-profit association “International Council for Amino Acid Science” (ICAAS) promotes research on the safe use of amino acids in human nutrition (e.g., Deutz et al 2017 ; McNeal et al 2018 ; Gheller et al 2020 ). In addition, ICAAS contributed to an assessment of purity standards of amino acids (Smriga 2020 ). The goal of this study was to evaluate the purity of nine globally available dietary supplement brands containing l -tryptophan (Trp), which were chosen due to the presumed links between Trp impurities and cases of eosinophilia-myalgia syndrome (EMS) (Varga et al 1992 ; Allen et al 2011 ).…”

“…The US National Institute of Health’s database of dietary labels (NIH 2021 ) revealed more than 800 different dietary supplements containing Trp at a dose equal to or below 0.5 g/day. A sub-chronic clinical safety trial (Hiratsuka et al 2013 ) determined that the upper limit of safe intake of supplemental Trp in normally fed adults was as high as 5.0 g/day, and thus this study assumed that the health risk (if any) of Trp supplementation was associated with impurities rather than overdosing (Smriga 2020 ). In addition to evaluating total impurities, liquid chromatography–mass spectrometry (LC–MS) was used to evaluate the presence of 1,1′-ethylidenebis- l -tryptophan (EBT), a toxic impurity previously linked to EMS outbreaks (Sidransky et al 1994 ).…”

Directed Discovery of Tetrapeptide Emulsifiers

“…Since the discovery by Reches and Gazit of the ability of diphenylalanine (FF) to self-assemble, ( Reches and Gazit, 2003 ), peptides have been increasingly investigated for their ability to structure materials. Of particular interest for the food and cosmetics industries is the GRAS (Generally Regarded As Safe) status of amino acids ( Smriga, 2020 ). However, the use of aromatic amino acids such as phenylalanine (F), tryptophan (W), and tyrosine (Y) is considered less desirable due to the propensity of these amino acids to form very stable supramolecular structures that can withstand metabolization.…”

PB@UiO-67-CDC-(CH3)2 as an Ultrasensitive Ratiometric Fluorescence Sensor: Visible “Turn-On” Effect for Detecting Preservatives and Amino Acids

“…For example, leucine can reduce protein hydrolysis, promote protein synthesis, and effectively improve the state of malnutrition and muscle loss . As a result, sensitive detection of amino acids can help people avoid the decline of immune function caused by ineffective dietary supplements. , Simultaneously, detecting excessive levels of preservatives will ensure food hygiene and avoid significant harm to the human body ascribed to improper levels in food …”