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Feature Papers in Proteins and Amino Acids in Relation to Human Health

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Proteins and Amino Acids".

Deadline for manuscript submissions: 5 April 2026 | Viewed by 28391

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Prof. Dr. Philip J. Atherton

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School of Medicine, Royal Derby Hospital, University of Nottingham, Nottingham, UK
Interests: skeletal muscle; nutrition; metabolism; protein synthesis; ageing; cell signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The purpose of this Special Issue is to highlight the functional role of dietary proteins and their amino acid constituents in the context of human health. This Special Issue, focusing primarily on human/clinical research, seeks original research papers and review articles (both narrative and systematic in nature) outlining the role(s) of proteins/amino acids in regulating metabolism across any tissue of the body in health, exercise, inactivity, and disease states. This Special Issue is relevant for observational and interventional trials, in addition to biomarker and bioactive compound-related research. Studies of human cell data derived from in vitro investigations of proteins, peptides, and amino acids are also within the scope of this Special Issue, as are studies using animal models, where the model’s translational reference to humans is clearly illustrated.

Prof. Dr. Philip J. Atherton
Guest Editor

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Keywords

health
disease
proteins
amino acids
cells
humans
biomarkers
bioactives

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Published Papers (8 papers)

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Research

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20 pages, 4450 KB

Open AccessArticle

Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration

by Hossameldin Abouhish, Lamiaa Shalaby, Omar Elzayat, Neelesh Peddireddy and Amany Tawfik

Nutrients 2026, 18(2), 236; https://doi.org/10.3390/nu18020236 - 12 Jan 2026

Viewed by 434

Abstract

Background/Objectives: Vitamin B₁₂ deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B₆, B₉, and B₁₂) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice. Methods: C57BL/6- Wild-type (WT) and cbs^+/− mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (−)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12–16 weeks, the success of the diet regimes was confirmed by observing serum B₁₂ deficiency in the B-Vit (−) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (−) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels. Results: The B-vitamin deficiency caused significant drop in serum vitamin B₁₂ and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation. Conclusions: a long-term deficiency of vitamins B₆, B₉, and B₁₂ can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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14 pages, 755 KB

Open AccessArticle

Investigating the Digestibility, Bioavailability and Utilization of Protein Blends in Older Adults Using a Dual Stable Isotope Tracer Technique

by Jake Cox, Bethan E. Phillips, James Bunce, Thomas Smart, Joshua Wall, Hannah Crossland, Daniel J. Wilkinson, Kenneth Smith and Philip J. Atherton

Nutrients 2025, 17(21), 3328; https://doi.org/10.3390/nu17213328 - 23 Oct 2025

Viewed by 1497

Abstract

Objectives: The impact of combining animal and plant protein sources on digestibility is unclear, despite their increasing clinical use. Using a non-invasive dual stable isotope tracer approach, we assessed the digestibility, bioavailability and utilization of distinct protein blends in older adults, and associated plasma amino acid profiles and muscle protein synthesis (MPS) rates. Methods: Thirty-two older men (69 ± 3 y) consumed one of four protein blends (A (51:49, casein/soy); B and C (35:25:20:20, whey/casein/soy/pea); D (80:20, casein/whey)) alongside primed constant infusions of [1,2-¹³C₂] leucine for 8 h. Arterialized blood and vastus lateralis muscle biopsies were collected during a trickle feed protocol with all blends providing 20 g total protein, universally labeled ¹³C-spirulina, and ²H-cell free amino acid mix to determine digestibility. This trial was registered at Clinicaltrials.gov (ID-NCT07038655). Results: No differences (¹³C:²H ratios) were found in digestibility between the protein blends (p > 0.05). Mean (±SEM) fed state MPS at 2.5 h was 0.078 ± 0.009%/h, 0.075 ± 0.012%/h, 0.085 ± 0.007%/h and 0.065 ± 0.011%/h for drinks A, B, C and D, respectively, with a main time effect observed (p < 0.01), but no significant differences between drinks. Plasma essential amino acids (EAAs) increased significantly from baseline for all blends by 40 min (p < 0.05), with no differences between blends at any time point. Conclusions: These findings suggest that protein quantity (and/or leucine content), rather than composition, appears to be the most important factor driving MPS. Future work should focus on clinical populations where protein requirements and digestibility characteristics may differ. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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16 pages, 2351 KB

Open AccessArticle

Associations Between Dietary Amino Acid Intake and Elevated High-Sensitivity C-Reactive Protein in Children: Insights from a Cross-Sectional Machine Learning Study

by Lianlong Yu, Xiaodong Zheng, Jilan Li, Changqing Liu, Yiya Liu, Meina Tian, Qianrang Zhu, Zhenchuang Tang and Maoyu Wu

Nutrients 2025, 17(13), 2235; https://doi.org/10.3390/nu17132235 - 5 Jul 2025

Viewed by 1818

Abstract

Background High-sensitivity C-reactive protein (hs-CRP) is a protein that indicates inflammation and the risk of cardiovascular diseases. The intake of dietary amino acids can influence immune and inflammatory reactions. However, studies on the relationship between dietary amino acids and hs-CRP, especially in children, remain scarce. Methods This cross-sectional study analyzed data from the Nutrition and China Children and Lactating Women Nutrition and Health Survey (2016–2019), focusing on 3514 children (724 with elevated hs-CRP ≥ 3 mg/L and 2790 with normal levels). Dietary information was gathered via a food frequency questionnaire, and hs-CRP levels were obtained from blood samples. Boruta algorithm and propensity scores were used to select and match dietary factors and sample sizes. Machine learning (ML) algorithms and logistic regression models assessed the link between amino acid intake and elevated hs-CRP risk, adjusting for age, sex, BMI, and lifestyle factors. Results The odds ratios (ORs) for elevated hs-CRP were significant for several amino acids, including Ile, Leu, Lys, Ser, Cys, Tyr, His, Pro, SAA, and AAA, with values ranging from 1.10 to 2.07. The LightGBM algorithm was the most effective in predicting elevated hs-CRP risk, achieving an AUC of 0.927. Tyrosine, methionine, cysteine, and proline were identified as important features by SHAP analysis and logistic regression. The intake of Ser, Cys, Tyr, and Pro showed a linear increase in the risk of elevated hs-CRP, especially in individuals with low protein intake and normal weight (p < 0.1). Conclusions Intake of amino acids like Ser, Cys, Tyr, and Pro significantly impacts hs-CRP levels in children, indicating that regulating these could help prevent inflammation-related diseases. This study supports future dietary and health management strategies. This is first large-scale ML study linking amino acids to pediatric inflammation in China. The main limitations are the cross-section design and the use of self-reported dietary data. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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21 pages, 1652 KB

Open AccessArticle

A Community-Based Mixed-Methods Study: Fish Bycatch Protein Supplementation as a Sustainable Solution for Child Malnutrition in Bengaluru, India

by Kristen P. Yang, Sunil K. Khanna, Angela Chaudhuri, Syama B. Syam and Tammy M. Bray

Nutrients 2025, 17(11), 1751; https://doi.org/10.3390/nu17111751 - 22 May 2025

Viewed by 2543

Abstract

Objective: Malnutrition remains a global challenge to child development, with urban slums in India experiencing high rates of protein deficiency. This study aimed to evaluate the effectiveness of a low-cost, fish bycatch-derived protein supplement in supporting catch-up growth among malnourished children. Methods: Using the Sustainable Community Partnership and Empowerment (SCOPE) model, we implemented a 90-day intervention with daily 10 g of Advanced Protein Powder (APP), produced from underutilized fish bycatch. Forty-six malnourished children (aged 3–6) from Bengaluru slums were randomized into a Control group receiving caloric support or an APP supplement group. Growth indicators, cognition, and caregiver perspectives were assessed. Results: Children receiving the APP supplement showed a significant increase in the weight-for-age percentile (underweight), rising by 7.59%, compared to 0.59% in the Control group (p = 0.02185). Muscle growth, measured by mid-upper arm circumference, also improved significantly in the APP Group (p < 0.05). In the first month, APP supplementation led to a significant height gain of 1.86 cm (p < 0.001), whereas the Control group showed no change (p > 0.05). Additionally, APP supplementation enhanced cognitive function, visual processing, short-term memory, and planning ability, with sustained effects at six months (p < 0.05). Caregivers reported noticeable improvements in children’s vitality, appetite, focus, and engagement in social and learning activities. Conclusions: Bycatch-derived protein supplementation, implemented through the SCOPE model, enhanced physical growth, behavior, and cognition in malnourished children in urban slums. Future studies should investigate the long-term effects, scalability, and adaptability of this sustainable solution for addressing child malnutrition. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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24 pages, 2140 KB

Open AccessReview

by Íñigo M. Pérez-Castillo, Ricardo Rueda, Suzette L. Pereira, Hakim Bouzamondo, José López-Chicharro, Felipe Segura-Ortiz and Philip J. Atherton

Nutrients 2025, 17(22), 3503; https://doi.org/10.3390/nu17223503 - 9 Nov 2025

Viewed by 5656

Abstract

Anabolic resistance, consisting of a diminished ability of aging muscle to respond to anabolic stimuli such as exercise and protein intake, is a key contributor to age-related declines in muscle mass. However, diseases and lifestyle factors associated with aging, including insulin resistance states, overweight/obesity, persistent inflammation and specifically—as a focus herein—physical inactivity and inadequate dietary protein-intake habits, might interact with chronological impairments in muscle anabolism. In this context, master athletes, as individuals who have engaged in lifelong structured exercise, including regular training and sports participation, offer a valuable model for studying processes of chronological vs. inactivity-related aging. While these lifelong exercisers may present improved body composition parameters and other potential benefits in terms of muscle mass and function, it remains unclear whether exercise practice throughout life can prevent the development of anabolic resistance associated with aging. Albeit limited, evidence has indicated that even in lifelong-trained older individuals there is a blunted post-exercise muscle anabolic response compared to younger athletes. However, there is a paucity of data to systematically understand the differences in postprandial anabolic response to varying protein doses in older vs. young athletes. In lieu of the above, it seems reasonable that master athletes may benefit from increasing protein intake closer to the upper limit of current recommendations (1.6–2.0 g/kg/day). In addition, supplementing their diet with ingredients that have established anabolic potential, including branched chain amino acids (BCAAs) such as leucine, the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), and n3-polyunsaturated fatty acids (n3-PUFA), may potentiate the anabolic response to protein and exercise. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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12 pages, 485 KB

Open AccessReview

Egg Yolk Immunoglobulins (IgY) Purification, Activity Enhancement, and Potential Benefits for Human Health

by Huilong Qiu, Xiaomin Jin, Xiaomei Zhang, Ke Chen, Lianshun Wang and Jiaqiang Huang

Nutrients 2025, 17(17), 2890; https://doi.org/10.3390/nu17172890 - 6 Sep 2025

Cited by 3 | Viewed by 5045

Abstract

With the rapid development of the laying hen industry and the continuous innovation of farming technology, egg production continues to increase. Eggs are rich in proteins, lipids, and immunoglobulins (IgY) found in the egg yolk. IgY can be used to treat human diseases and prevent bacterial and viral infections. In addition, IgY has advantages over IgG in biological structure and function and is characterized by high specificity, safety, yield, and economic efficiency. This review describes the basic structure and properties of IgY, lists a variety of IgY purification methods, and outlines measures to maintain and enhance its activity, focusing on the current status of its research in immunoprevention and treatment of human diseases and outlines its importance, and finally proposes the current challenges and future research priorities of IgY in the field of biomedical research to provide a scientific basis for the wide range of applications of IgY in human health. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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17 pages, 666 KB

Open AccessReview

Three Major Deficiency Diseases Harming Mankind (Protein, Retinoid, Iron) Operate Under Tryptophan Dependency

by Yves Ingenbleek

Nutrients 2025, 17(15), 2505; https://doi.org/10.3390/nu17152505 - 30 Jul 2025

Cited by 1 | Viewed by 1793

Abstract

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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25 pages, 1923 KB

Open AccessEditor’s ChoiceReview

Proteins and Amino Acids from Edible Insects for the Human Diet—A Narrative Review Considering Environmental Sustainability and Regulatory Challenges

by Lukas Nachtigall, Tilman Grune and Daniela Weber

Nutrients 2025, 17(7), 1245; https://doi.org/10.3390/nu17071245 - 2 Apr 2025

Cited by 17 | Viewed by 7600

Abstract

The scientific interest in edible insects as an alternative source of high-value protein for the human diet has increased drastically over the last decade. Edible insects harbour enormous potential in terms of planetary health. Their lower water and land use, lower feed conversion ratios, and overall lower global warming potential paired with a high nutritional value compared with conventional livestock are key drivers towards an environmentally sustainable diet. However, low consumer acceptance, as well as regulatory challenges, have slowed down the success of edible insects in Western countries, despite edible insects being consumed regularly all over the world. To date, four edible insect species have been approved as novel foods in the European Union—namely yellow mealworm (Tenebrio molitor), migratory locust (Locusta migratoria), house cricket (Acheta domesticus), and lesser mealworm (Alphitobius diaperinus). Depending on the species, they have a high protein content (48–67%), with a beneficial indispensable amino acid profile, high fat content (21–39%), with a high content of unsaturated fatty acids based on the dry matter, and contain reasonable amounts of minerals and vitamins. Unlike other animal-based foods, edible insects contain dietary fibre. Data on the bioavailability of nutrients in humans are scarce. Although numerous publications have investigated the nutritional profiles, environmental impacts, and future perspectives of edible insects, here, those findings are reviewed critically, as some publications were partially contradictory or related to selected species only. In this narrative review, we emphasise that edible insects could play a key role in a changing world with a steadily increasing demand for nutritionally valuable food and the depletion of natural resources. Full article

(This article belongs to the Special Issue Feature Papers in Proteins and Amino Acids in Relation to Human Health)

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