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Special Issue "Amino Acid Nutrition and Metabolism in Health and Disease"

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 101369

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Special Issue Editor

Dr. Adam Rose

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Guest Editor

Nutrient Metabolism and Signalling Laboratory, Metabolic Disease and Obesity Programme, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia
Interests: amino acid nutrition; inter-organ nutrition; amino acid metabolism; diabetes; endocrinology; stress

Special Issue Information

Dear colleagues,

This Special Issue of Nutrients, entitled “Amino Acid Nutrition and Metabolism in Health and Disease”, welcomes the submission of manuscripts either describing original research or reviewing the scientific literature. Manuscripts should focus on amino acid nutrition particularly as it influences particular life-stage phenotypes/outcomes, as well as certain diseases such as the major modern chronic diseases such as type 2 diabetes, cardiovascular disease, neurodegeneration, and even cancer.

Topics must have a clear focus on amino acid nutrition and metabolism. Potential topics may include, but are not limited to, the following:

Cellular signalling mechanisms in amino acid nutrition and metabolism
The role of amino acid transport and metabolism in metabolic control
Hormonal mechanisms linking amino acid nutrition and related phenotypes
Inter-organ and/or tissue niche-amino-acid metabolism
Amino acid nutrition and metabolism, developmental programming, and epigenomics
Amino acid nutrition and metabolism in ageing and age-related diseases
Amino acid nutrition, gastrointestinal health, and gut microbiome

Dr. Adam J. Rose
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 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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 acid
nutrition
metabolism
signalling
hormones
essential amino acid
non-essential amino acid
transport
hormones
tissue niche
crosstalk
gut health
cancer
diabetes
neurodegeneration
healthspan

Published Papers (13 papers)

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Research

Jump to: Review

16 pages, 3407 KiB

Open AccessArticle

Mice Lacking the Intestinal and Renal Neutral Amino Acid Transporter SLC6A19 Demonstrate the Relationship between Dietary Protein Intake and Amino Acid Malabsorption

Kiran Javed

and

Stefan Bröer

Nutrients 2019, 11(9), 2024; https://doi.org/10.3390/nu11092024 - 29 Aug 2019

Cited by 20 | Viewed by 4484

Abstract

Dietary protein restriction has beneficial impacts on metabolic health. B⁰AT1 (SLC6A19) is the major transporter of neutral amino acids at the intestinal epithelia and absorbs the bulk of the diet-derived neutral amino acids from the intestinal lumen. It also reabsorbs neutral amino acids in the renal proximal tubules. Mice lacking B⁰AT1 show cellular outcomes of protein restriction, such as high FGF21 levels and low mTORC1 activity. Moreover, they have improved glucose homeostasis and resist diet-induced obesity. In this study, we investigated the relationship between protein restriction and dietary protein intake in C57Bl6/J wild-type (wt) and SLC6A19-knockout (SLC6A19ko) mice. When SLC6A19ko mice were fed diets containing 5%, 25%, or 52% of their total calories derived from protein, no differences in food intake or weight gain were observed. All essential amino acids significantly positively correlated with increasing dietary casein content in the wt mice. The SLC6A19ko mice showed reduced postprandial levels of essential amino acids in plasma, particularly following high-protein diets. Upon fasting, essential amino acids were the same in the wt and SLC6A19ko mice due to reduced amino acid catabolism. Bacterial metabolites originating from amino acid fermentation correlated with the dietary protein content, but showed a complex profile in the blood of the SLC6A19ko mice. This study highlights the potential of SLC6A19 as a knock-out or inhibition target to induce protein restriction for the treatment of metabolic disorders. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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13 pages, 525 KiB

Open AccessCommunication

Role of Peptide Hormones in the Adaptation to Altered Dietary Protein Intake

Adam J. Rose

Nutrients 2019, 11(9), 1990; https://doi.org/10.3390/nu11091990 - 23 Aug 2019

Cited by 7 | Viewed by 5509

Abstract

Dietary protein profoundly influences organismal traits ultimately affecting healthspan. While intracellular signalling downstream of altered amino acid supply is undoubtedly important, peptide hormones have emerged as critical factors determining systemic responses to variations in protein intake. Here the regulation and role of certain [...] Read more.

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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11 pages, 1404 KiB

Open AccessArticle

Of Older Mice and Men: Branched-Chain Amino Acids and Body Composition

Rosilene V. Ribeiro

Samantha M. Solon-Biet

, John O’Sullivan, Yen Chin Koay,

, Vasi Naganathan,

and David G Le Couteur

Nutrients 2019, 11(8), 1882; https://doi.org/10.3390/nu11081882 - 13 Aug 2019

Cited by 18 | Viewed by 4451

Abstract

Protein and branched-chain amino acid (BCAA) intake are associated with changes in circulating BCAAs and influence metabolic health in humans and rodents. However, the relationship between BCAAs and body composition in both species is unclear, with many studies questioning the translatability of preclinical findings to humans. Here, we assessed and directly compared the relationship between circulating BCAAs, body composition, and intake in older mice and men. Body weight and body fat were positively associated with circulating BCAA levels in both mouse and human, which remained significant after adjustments for age, physical activity, number of morbidities, smoking status, and source of income in the human cohort. Macronutrient intakes were similarly associated with circulating BCAA levels; however, the relationship between protein intake and BCAAs were more pronounced in the mice. These findings indicate that the relationship between circulating BCAAs, body composition, and intakes are comparable in both species, suggesting that the mouse is an effective model for examining the effects of BCAAs on body composition in older humans. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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14 pages, 1054 KiB

Open AccessCommunication

The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure

and

Nutrients 2019, 11(7), 1679; https://doi.org/10.3390/nu11071679 - 22 Jul 2019

Cited by 73 | Viewed by 25552

Abstract

Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (K_m) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the “l-arginine paradox”. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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Graphical abstract

12 pages, 766 KiB

Open AccessArticle

Combined Effect of Arginine, Valine, and Serine on Exercise-Induced Fatigue in Healthy Volunteers: A Randomized, Double-Blinded, Placebo-Controlled Crossover Study

and

Nutrients 2019, 11(4), 862; https://doi.org/10.3390/nu11040862 - 17 Apr 2019

Cited by 16 | Viewed by 4616

Abstract

Although several kinds of amino acids (AAs) are known to affect physiological actions during exercise, little is known about the combined effects of a mixture of several AAs on fatigue during exercise. The aim of the present study was to investigate the effect of an AA mixture supplement containing arginine, valine, and serine on exercise-induced fatigue in healthy volunteers. These AAs were selected because they were expected to reduce fatigue during exercise by acting the positive effects synergistically. A randomized, double-blinded, placebo-controlled crossover trial was conducted. Thirty-nine males ingested an AA mixture containing 3600 mg of arginine, 2200 mg of valine, and 200 mg of serine or a placebo each day for 14 days. On the 14th day, the participants completed an exercise trial on a cycle ergometer at 50% of VO₂max for 120 min. After the two-week washout period, the participants repeated the same trial with the other test sample. The participant’s feeling of fatigue based on a visual analog scale (VAS) and a rating of perceived exertion (RPE), as well as blood and physical parameters were evaluated. The feeling of fatigue based on VAS and RPE were significantly improved in AA compared to those in placebo. In the blood analysis, the increase in serum total ketone bodies during exercise and plasma tryptophan/branched-chain amino acids were significantly lower in AA than those in placebo. The present study demonstrated that supplementation with an AA mixture containing arginine, valine, and serine reduced the feeling of fatigue during exercise. The AA mixture also changed several blood parameters, which may contribute to the anti-fatigue effect. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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13 pages, 2692 KiB

Open AccessArticle

Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model

Jérémie David

Dominique Dardevet

Laurent Mosoni

Isabelle Savary-Auzeloux

and

Sergio Polakof

Nutrients 2019, 11(2), 355; https://doi.org/10.3390/nu11020355 - 08 Feb 2019

Cited by 23 | Viewed by 4089

Abstract

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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16 pages, 3686 KiB

Open AccessArticle

Plasma Sulphur-Containing Amino Acids, Physical Exercise and Insulin Sensitivity in Overweight Dysglycemic and Normal Weight Normoglycemic Men

and

Nutrients 2019, 11(1), 10; https://doi.org/10.3390/nu11010010 - 20 Dec 2018

Cited by 24 | Viewed by 6859

Abstract

Plasma sulphur-containing amino acids and related metabolites are associated with insulin sensitivity, although the mechanisms are unclear. We examined the effect of exercise on this relationship. Dysglycemic (n = 13) and normoglycemic (n = 13) men underwent 45 min cycling before and after 12 weeks exercise intervention. We performed hyperinsulinemic euglycemic clamp, mRNA-sequencing of skeletal muscle and adipose tissue biopsies, and targeted profiling of plasma metabolites by LC-MS/MS. Insulin sensitivity increased similarly in dysglycemic and normoglycemic men after 12 weeks of exercise, in parallel to similar increases in concentration of plasma glutamine, and decreased concentrations of plasma glutamate, cysteine, taurine, and glutathione. Change in plasma concentrations of cysteine and glutathione exhibited the strongest correlations to exercise-improved insulin sensitivity, and expression of a cluster of genes essential for oxidative phosphorylation and fatty acid metabolism in both skeletal muscle and adipose tissue, as well as mitochondria-related genes such as mitofilin. Forty-five min of cycling decreased plasma concentrations of glutamine and methionine, and increased plasma concentrations of glutamate, homocysteine, cystathionine, cysteine, glutathione, and taurine. Similar acute responses were seen in both groups before and after the 12 weeks training period. Both acute and long-term exercise may influence transsulphuration and glutathione biosynthesis, linking exercise-improved insulin sensitivity to oxidative stress and mitochondrial function. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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15 pages, 489 KiB

Open AccessArticle

Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial

and

Nutrients 2018, 10(12), 1822; https://doi.org/10.3390/nu10121822 - 23 Nov 2018

Cited by 32 | Viewed by 6140

Abstract

Dietary and plasma total cysteine (tCys) have been associated with adiposity, possibly through interaction with stearoyl–CoA desaturase (SCD), which is an enzyme that is involved in fatty acid and energy metabolism. We evaluated the effect of a dietary intervention with low cysteine and methionine and high polyunsaturated fatty acids (PUFAs) on plasma and urinary sulfur amino acids and SCD activity indices. Fourteen normal-weight healthy subjects were randomized to a seven-day diet low in cysteine and methionine and high in PUFAs (Cys/Met_low + PUFA), or high in saturated fatty acids (SFA), cysteine, and methionine (Cys/Met_high + SFA). Compared with the Cys/Met_high + SFA group, plasma methionine and cystathionine decreased (p-values < 0.05), whereas cystine tended to increase (p = 0.06) in the Cys/Met_low + PUFA group. Plasma total cysteine (tCys) was not significantly different between the groups. Urinary cysteine and taurine decreased in the Cys/Met_low + PUFA group compared with the Cys/Met_high + SFA group (p-values < 0.05). Plasma SCD-activity indices were not different between the groups, but the change in cystine correlated with the SCD-16 index in the Cys/Met_low + PUFA group. A diet low in methionine and cysteine decreased plasma methionine and urinary cysteine and taurine. Plasma tCys was unchanged, suggesting that compensatory mechanisms are activated during methionine and cysteine restriction to maintain plasma tCys. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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12 pages, 682 KiB

Open AccessArticle

Isolated Soy Protein Supplementation and Exercise Improve Fatigue-Related Biomarker Levels and Bone Strength in Ovariectomized Mice

and

Nutrients 2018, 10(11), 1792; https://doi.org/10.3390/nu10111792 - 17 Nov 2018

Cited by 19 | Viewed by 5603

Abstract

Isolated soy protein (ISP) is a well-known supplement and has been reported to improve health, exercise performance, body composition, and energy utilization. ISP exhibits multifunctional bioactivities and also contains branched-chain amino acids (BCAAs), which have been confirmed to positively affect body weight (BW) regulation and muscle protein synthesis. The combined effects of BCAA supplements and exercise in older postmenopausal women with osteoporosis, sarcopenia, and obesity have been inadequately investigated. Therefore, in this study, we evaluated the potential beneficial effects of soy protein supplementation and exercise training on postmenopausal mice. Forty mice (14 weeks old) with ovariectomy-induced osteosarcopenic obesity were divided into five groups (n = 8), namely sham ovariectomy (OVX, control), OVX, OVX with ISP supplementation (OVX+ISP), OVX with exercise training (ET, OVX+ET), and OVX with ISP and ET (OVX+ISP+ET). The mice received a vehicle or soy protein (3.8 g/kg BW) by oral gavage for four weeks, and the exercise performance (forelimb grip strength and exhaustive swimming time) was evaluated. In the biochemical profiles, we evaluated the serum glucose level and tissue damage markers, such as lactate, ammonia, glucose, blood urine nitrogen (BUN), and creatinine phosphate kinase (CPK). The body composition was determined by evaluating bone stiffness and muscle mass. All data were analyzed using one-way repeated measures analysis of variance. The physical performance of the OVX+ISP+ET group did not differ from that of the other groups. The OVX+ISP+ET group exhibited lower levels of serum lactate, ammonia, CPK, and BUN as well as economized glucose metabolism after an acute exercise challenge. The OVX+ISP+ET group also exhibited higher muscle mass and bone strength than the OVX group. Our study demonstrated that a combination of ISP supplementation and exercise reduced fatigue and improved bone function in OVX mice. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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Review

Jump to: Research

18 pages, 668 KiB

Open AccessReview

d-amino Acids in Health and Disease: A Focus on Cancer

Jacco J.A.J. Bastings

Hans M. van Eijk

Steven W. Olde Damink

and

Sander S. Rensen

Nutrients 2019, 11(9), 2205; https://doi.org/10.3390/nu11092205 - 12 Sep 2019

Cited by 88 | Viewed by 9900

Abstract

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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15 pages, 2809 KiB

Open AccessReview

Impact of Arginine Nutrition and Metabolism during Pregnancy on Offspring Outcomes

Chien-Ning Hsu

and

You-Lin Tain

Nutrients 2019, 11(7), 1452; https://doi.org/10.3390/nu11071452 - 27 Jun 2019

Cited by 33 | Viewed by 8870

Abstract

By serving as a precursor for the synthesis of nitric oxide, polyamines, and other molecules with biological importance, arginine plays a key role in pregnancy and fetal development. Arginine supplementation is a potential therapy for treating many human diseases. An impaired arginine metabolic pathway during gestation might produce long-term morphological or functional changes in the offspring, namely, developmental programming to increase vulnerability to developing a variety of non-communicable diseases (NCDs) in later life. In contrast, reprogramming is a strategy that shifts therapeutic interventions from adulthood to early-life, in order to reverse the programming processes, which might counterbalance the rising epidemic of NCDs. This review presented the role of arginine synthesis and metabolism in pregnancy. We also provided evidence for the links between an impaired arginine metabolic pathway and the pathogenesis of compromised pregnancy and fetal programming. This was followed by reprogramming strategies targeting the arginine metabolic pathway, to prevent the developmental programming of NCDs. Despite emerging evidence from experimental studies showing that targeting the arginine metabolic pathway has promise as a reprogramming strategy in pregnancy to prevent NCDs in the offspring, these results need further clinical application. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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14 pages, 753 KiB

Open AccessReview

Dietary Sulfur Amino Acid Restriction and the Integrated Stress Response: Mechanistic Insights

William O. Jonsson

Nicholas S. Margolies

and

Tracy G. Anthony

Nutrients 2019, 11(6), 1349; https://doi.org/10.3390/nu11061349 - 15 Jun 2019

Cited by 23 | Viewed by 6846

Abstract

Dietary sulfur amino acid restriction, also referred to as methionine restriction, increases food intake and energy expenditure and alters body composition in rodents, resulting in improved metabolic health and a longer lifespan. Among the known nutrient-responsive signaling pathways, the evolutionary conserved integrated stress response (ISR) is a lesser-understood candidate in mediating the hormetic effects of dietary sulfur amino acid restriction (SAAR). A key feature of the ISR is the concept that a family of protein kinases phosphorylates eukaryotic initiation factor 2 (eIF2), dampening general protein synthesis to conserve cellular resources. This slowed translation simultaneously allows for preferential translation of genes with special sequence features in the 5′ leader. Among this class of mRNAs is activating transcription factor 4 (ATF4), an orchestrator of transcriptional control during nutrient stress. Several ATF4 gene targets help execute key processes affected by SAAR such as lipid metabolism, the transsulfuration pathway, and antioxidant defenses. Exploration of the canonical ISR demonstrates that eIF2 phosphorylation is not necessary for ATF4-driven changes in the transcriptome during SAAR. Additional research is needed to clarify the regulation of ATF4 and its gene targets during SAAR. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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16 pages, 2849 KiB

Open AccessReview

Dietary Protein and Amino Acid Intake: Links to the Maintenance of Cognitive Health

Jordan M. Glenn

Erica N. Madero

and

Nick T. Bott

Nutrients 2019, 11(6), 1315; https://doi.org/10.3390/nu11061315 - 12 Jun 2019

Cited by 37 | Viewed by 7542

Abstract

With the rapid growth in the aging population, there has been a subsequent increase in the rates of Alzheimer’s disease and related dementias (ADRD). To combat these increases in ADRD, scientists and clinicians have begun to place an increased emphasis on preventative methods to ameliorate disease rates, with a primary focus area on dietary intake. Protein/amino acid intake is a burgeoning area of research as it relates to the prevention of ADRD, and consumption is directly related to a number of disease-related risk factors as such low-muscle mass, sleep, stress, depression, and anxiety. As a result, the role that protein/amino acid intake plays in affecting modifiable risk factors for cognitive decline has provided a robust area for scientific exploration; however, this research is still speculative and specific mechanisms have to be proven. The purpose of this review is to describe the current understanding of protein and amino acids and the preventative roles they play with regard to ADRD, while providing future recommendations for this body of research. Additionally, we will discuss the current recommendations for protein intake and how much protein older adults should consume in order to properly manage their long-term risk for cognitive decline. Full article

(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism in Health and Disease)

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