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Nutrients
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Relevance and Safe Utilization of Amino Acids in Dietary Supplements
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Relevance and Safe Utilization of Amino Acids in Dietary Supplements

A Special Issue of Nutrients (ISSN 2072-6643) belonging to the section "Proteins and Amino Acids".

Deadline for manuscript submissions: 20 December 2026 | Viewed by 9750

Editor

Dr. François Blachier

E-Mail Website
Guest Editor
UMR-PNCA, Université Paris-Saclay, AgroParisTech, INRAE, 91120 Palaiseau, France
Interests: nutrition; amino acid gastroenterology; nitrogen metabolism; proteins

Special Issue Information

Dear Colleagues,

We present a Special Issue of Nutrients on the “Relevance and Safe Utilization of Amino Acids in Dietary Supplements”.

Amino acid supplementation may be recommended in healthy individuals who present with a deficiency of one or more amino acids in the dietary proteins that humans consume. Clinical and experimental studies also focus on specific physiological and pathophysiological situations where the requirement for specific amino acids increases, such as attaining optimal metabolic and physiological functions.

However, there is a major concern regarding supplements with amino acid contents above the tolerable upper intake level (UL), defined as the highest level of daily amino acid intake that is likely to pose no adverse effects on consumer health.

Based on this context, we invite contributions to this Nutrients SI which will gather original reports from clinical trials aimed at documenting the efficiency of supplementation with specific amino acids in different situations, as well as the doses of specific amino acids which must not be exceeded in supplements for user safety. Original reports from experimental studies deciphering the mechanisms involved and the effects of amino acid supplements are also welcome. Contributors are encouraged to submit review papers dedicated to these topics.

I look forward to receiving your contribution.

Dr. François Blachier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • amino acids
  • dietary supplements
  • tolerable upper intake level
  • physiological relevance
  • pathophysiology

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Published Papers (3 papers)

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Research

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17 pages, 1494 KB  
Article
Investigating the Impact of Protein Supplementation from Different Sources on Advanced Glycation End Products in Older Adults in Singapore Following a Healthy Dietary Pattern
by Marcus Ting, Ian En Kai Mak, Yueying Yao, Amelia Shan Mei Chng, Chin Meng Khoo and Jung Eun Kim
Nutrients 2026, 18(17), 2925; https://doi.org/10.3390/nu18172925 - 7 Sep 2026
Viewed by 514
Abstract
Background/Objectives: Protein supplementation may elevate advanced glycation end products (AGEs) through higher dietary AGE (dAGE) content and increase amino acid-driven endogenous formation. Protein supplementation from different sources may differentially affect AGE levels, possibly through differences in amino acid composition, digestion and metabolism, but [...] Read more.
Background/Objectives: Protein supplementation may elevate advanced glycation end products (AGEs) through higher dietary AGE (dAGE) content and increase amino acid-driven endogenous formation. Protein supplementation from different sources may differentially affect AGE levels, possibly through differences in amino acid composition, digestion and metabolism, but evidence from randomized controlled trials (RCTs) remains limited. This study aimed to examine the effect of protein supplementation from either casein (animal-based) or soy (plant-based) protein isolates on circulating, skin, and dAGE levels in older adults following a healthy dietary pattern (HDP). Methods: In this 16-week RCT, 55 older adults (mean age: 66 years old) in Singapore were assigned either to control (no supplementation), casein protein isolate supplementation, or soy protein isolate supplementation. This study was registered at clinicaltrials.gov as NCT05400005. Results and Discussion: Overall, there were no alterations in dietary, skin and total circulating AGE levels after protein supplementation when adhering to an HDP such as My Healthy Plate (MHP). However, different sources of protein supplementation resulted in differential changes in specific plasma AGE markers. Two-way ANOVA analysis showed that soy protein supplementation led to a significant increase in plasma N(6)-(1-carboxymethyl)-L-lysine (CML) compared to the other groups (week 0: 0.72 ± 0.10, week 16: 0.80 ± 0.10, pint = 0.040), while a paired t-test showed that casein protein supplementation led to a significant within-group increase in plasma pentosidine (week 0: 0.77 ± 0.06, week 16: 0.80 ± 0.05, p-value = 0.045). Other AGEs showed no significant changes. Conclusions: Protein supplementation while adhering to MHP did not significantly influence overall circulating and skin AGEs in older adults in Singapore. A differential response was observed only for plasma CML levels with soy protein supplementation, whereas the within-group increase in plasma pentosidine following casein supplementation should be interpreted with caution and requires further investigation. Full article
(This article belongs to the Special Issue Relevance and Safe Utilization of Amino Acids in Dietary Supplements)
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18 pages, 1893 KB  
Article
Evaluation of the Safety and Tolerability of L-Tyrosine Supplementation in Healthy Adult Men: A Randomized Crossover Trial
by Hideki Matsumoto, Naoki Miura, Masaki Naito and Rajavel Elango
Nutrients 2026, 18(12), 2020; https://doi.org/10.3390/nu18122020 - 21 Jun 2026
Viewed by 2031
Abstract
Background: L-tyrosine, classified as a dispensable amino acid, is widely consumed as a component of commonly consumed foods and as a dietary supplement. However, 4-week safety data on supplementation with this amino acid remain limited. Methods: The aim of this study was to [...] Read more.
Background: L-tyrosine, classified as a dispensable amino acid, is widely consumed as a component of commonly consumed foods and as a dietary supplement. However, 4-week safety data on supplementation with this amino acid remain limited. Methods: The aim of this study was to evaluate the safety and tolerability of L-tyrosine supplementation over a 4-week period and to estimate the no-observed-adverse-effect level (NOAEL). In a randomized, double-blind, placebo-controlled crossover trial, 30 healthy adult men received L-tyrosine at graded daily doses (0, 1, 2, 3, or 4 g/day). Each participant received four of the five doses in a randomized sequence, with each intervention period separated by a 2-week washout period. The primary endpoints were clinical laboratory parameters, and the secondary endpoint was the incidence of adverse events. Anthropometric and dietary parameters were also assessed. In addition, plasma amino acid concentrations following L-tyrosine supplementation were evaluated as exploratory outcomes. Results: No clinically meaningful or statistically significant dose-related abnormalities were observed in hematological, biochemical, or electrolyte parameters at any dose. Anthropometric and dietary parameters remained unchanged. No serious adverse events occurred, and the incidence of mild-to-moderate adverse events was comparable to that observed with placebo. At the end of each supplementation period and under fasting conditions, plasma L-tyrosine concentrations modestly increased at the highest dose (4 g/day), whereas concentrations of other amino acids remained unchanged. Conclusions: Four-week supplementation with L-tyrosine at doses up to 4 g/day was well tolerated in healthy adult men and was not associated with biochemical and clinically relevant adverse effects under the conditions of this study. These findings suggest that 4 g/day represents the highest tested intake level without observable adverse effects and may serve as the NOAEL under the present 4-week study conditions. Full article
(This article belongs to the Special Issue Relevance and Safe Utilization of Amino Acids in Dietary Supplements)
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Review

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33 pages, 1456 KB  
Review
Relevance and Safe Utilization of Amino Acids in Supplements for Human Nutrition: Lessons from Clinical and Preclinical Studies
by François Blachier
Nutrients 2026, 18(2), 296; https://doi.org/10.3390/nu18020296 - 17 Jan 2026
Cited by 2 | Viewed by 6538
Abstract
Amino acid availability is central for the synthesis of macromolecules and numerous bioactive compounds. Amino acids are also involved in ATP production, cell signaling, and the epigenetic regulation of gene expression in human cells. From clinical and experimental studies, it appears that supplementation [...] Read more.
Amino acid availability is central for the synthesis of macromolecules and numerous bioactive compounds. Amino acids are also involved in ATP production, cell signaling, and the epigenetic regulation of gene expression in human cells. From clinical and experimental studies, it appears that supplementation with specific amino acids may be relevant to correct for amino acid deficiency in the case of insufficient supply from dietary proteins with regards to the amounts needed for optimal metabolism and physiological functions. Clinical and experimental arguments suggest that amino acid supplementation may be indicated in specific situations under a specific nutritional context. However, it is essential not to overdose with excessive quantities of amino acids in supplements beyond the upper levels of safe intake (ULSI). In this narrative review, I recapitulate the protein and amino acid requirements for the general population and for subgroups of the population, and these requirements are compared to the usual consumption. Typical examples of clinical trials showing the benefits from amino acid supplementation in different physiological and pathophysiological contexts are presented together with results obtained from experimental studies. Parameters such as the no-observed-adverse-effect-level (NOAEL) values used to determine the ULSI for amino acid supplementation are defined, and values determined in clinical trials are given and discussed. Finally, prospects for future research in the field are proposed. Full article
(This article belongs to the Special Issue Relevance and Safe Utilization of Amino Acids in Dietary Supplements)
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