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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (25 November 2024) | Viewed by 23335

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Dr. Andrea Domenico Praticò

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Unit of Pediatrics, Department of Medicine and Surgery, University Kore of Enna, Cittadella Universitaria, 94100 Enna, Italy
Interests: child neurology; neurocutaneous disorders; immune-mediated disease of the central and peripheral nervous system; epilepsy; neurogenetics; movement disorders
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Dear Colleagues,

Many epidemiologic studies report a protective association between a balanced and adequate diet and cognitive impairment, brain health and neurodegenerative diseases. At the same time, data from clinical trials supporting these observational findings are also emerging, in particular in childhood and neonatal ages.

The neuroprotective properties may be linked directly to caloric restrictions or to some neuroprotective properties of food (in long-chain-polyunsaturated fatty acids, vitamin E and mineral elements).

Preventive interventions on neuroinflammation seem to be able to interfere with neurodegeneration, enhancing antioxidative defense, and lowering the risk and incidence of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases. It should be noticed that dietary supplementation-based strategies have been demonstrated to be effective in subjects with mild cognitive impairment, or directly in metabolic disorders in whom a specific enzymatic deficit may require specific dietary restrictions.

In some studies, adjunctive supplementation has also been demonstrated to improve depression, this being of marked benefit considering the comorbidity between cognitive impairment/dementia and depression

Dr. Andrea Domenico Praticò
Guest Editor

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Keywords

neurological disorders
neurodegenerative disorders
diet
food
free radicals
anti-oxidants

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Published Papers (11 papers)

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Editorial

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5 pages, 189 KiB

Open AccessEditorial

Therapeutic Opportunities for Food Supplements in Neurodegenerative Diseases

by Andrea D. Praticò

Nutrients 2025, 17(9), 1527; https://doi.org/10.3390/nu17091527 - 30 Apr 2025

Abstract

Neurodegenerative diseases (NDs) constitute a group of debilitating conditions characterized by the progressive loss of the structure and function of neurons in the central nervous system [...] Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

Research

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24 pages, 5204 KiB

Open AccessArticle

Omega-3 EPA Supplementation Shapes the Gut Microbiota Composition and Reduces Major Histocompatibility Complex Class II in Aged Wild-Type and APP/PS1 Alzheimer’s Mice: A Pilot Experimental Study

by Barbara Altendorfer, Ariane Benedetti, Heike Mrowetz, Sabine Bernegger, Alina Bretl, Julia Preishuber-Pflügl, Diana Marisa Bessa de Sousa, Anja Maria Ladek, Andreas Koller, Pauline Le Faouder, Justine Bertrand-Michel, Andrea Trost and Ludwig Aigner

Nutrients 2025, 17(7), 1108; https://doi.org/10.3390/nu17071108 - 21 Mar 2025

Viewed by 557

Abstract

Background/Objectives: Neuroinflammation, a hallmark of Alzheimer’s disease (AD), is characterized by elevated levels of inflammatory signaling molecules, including cytokines and eicosanoids, as well as increased microglial reactivity, and is augmented by gut microbiota dysbiosis via the gut–brain axis. We conducted a pilot experiment to elucidate the anti-inflammatory effects of dietary omega-3 polyunsaturated fatty acid (ω-3 PUFA) eicosapentaenoic acid (EPA) on the gut microbiota and neuroinflammation. Methods: Female APP/PS1 mice (TG) and non-transgenic littermates (WT), 13–14 months old, were fed a diet supplemented with 0.3% EPA or control chow for 3 weeks. The gut microbiota composition, hippocampal and plasma eicosanoids levels, platelet activation, and microglial phagocytosis, as well as the brain and retinal genes and protein expression, were analyzed. Results: EPA supplementation decreased the percentage of Bacteroidetes and increased bacteria of the phylum Firmicutes in APP/PS1 and WT mice. Inflammatory lipid mediators were elevated in the hippocampus of the TG mice, accompanied by a reduction in the endocannabinoid docosahexaenoyl ethanolamide (DHEA). Dietary EPA did not affect hippocampal lipid mediators, but reduced the levels of arachidonic-derived 5-HETE and N-arachidonoylethanolamine (AEA) in WT plasma. Moreover, EPA supplementation decreased major histocompatibility complex class II (MHCII) gene expression in the retina in both genotypes, and MHCII+ cells in the hippocampus of TG mice. Conclusions: This pilot study showed that short-term EPA supplementation shaped the gut microbiota by increasing butyrate-producing bacteria of the Firmicutes phylum and decreasing Gram-negative LPS-producing bacteria of the Bacteroidetes phylum, and downregulated the inflammatory microglial marker MHCII in two distinct regions of the central nervous system (CNS). Further investigation is needed to determine whether EPA-mediated effects on the microbiome and microglial MHCII have beneficial long-term effects on AD pathology and cognition. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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17 pages, 1063 KiB

Open AccessArticle

Genotype–Phenotype Correlation in a Large Cohort of Eastern Sicilian Patients Affected by Phenylketonuria: Newborn Screening Program, Clinical Features, and Follow-Up

by Maria Chiara Consentino, Luisa La Spina, Concetta Meli, Marianna Messina, Manuela Lo Bianco, Annamaria Sapuppo, Maria Grazia Pappalardo, Riccardo Iacobacci, Alessia Arena, Michele Vecchio, Martino Ruggieri, Agata Polizzi and Andrea Domenico Praticò

Nutrients 2025, 17(3), 379; https://doi.org/10.3390/nu17030379 - 21 Jan 2025

Viewed by 915

Abstract

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to impaired amino acid metabolism. Early diagnosis through newborn screening (NBS) enables prompt treatment, preventing neurological complications. This study aims to describe the genetic and phenotypic spectrum of PKU and mild hyperphenylalaninemia (m-HPA) in patients diagnosed at the Department of Inborn Errors of Metabolism and Newborn Screening, Hospital G. Rodolico-S. Marco, Catania, over four decades (1987–2023). Materials and Methods: The retrospective analysis included 102 patients with elevated blood phenylalanine (Phe) levels born in Sicily and followed at the Institute. The phenotype evaluation comprised the Phe levels at birth/diagnosis, dietary tolerance, and sapropterin dihydrochloride responsiveness. The dietary compliance and Phe/Tyr ratios were assessed and compared across phenotypic classes and age groups. Results: Of 102 patients, 34 were classified as having classic PKU, 9 as having moderate PKU, 26 as having mild PKU, and 33 as having m-HPA, with a median age of 21.72 years. Common PAH variants included c.1066-11G>A (26/204 alleles), c.782G>A (18/204 alleles), and c.165delT (13/204 alleles). The phenotypes sometimes diverged from the genotype predictions, emphasizing dietary tolerance over the initial Phe levels for classification: m-HPA was statistically associated with a higher dietary tolerance (p < 0.001) compared to the classic, moderate, or mild forms of PKU. Conclusions: This study highlights the importance of large databases (e.g., BioPKU) for phenotype prediction and treatment optimization. Regular assessment of Phe/Tyr ratios is crucial for monitoring adherence and health. Phenotype determination, dietary management, and emerging therapies (Pegvaliase and gene therapy) are key to improving outcomes for PKU patients. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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9 pages, 232 KiB

Open AccessArticle

The Impact of Vitamin D Supplementation Duration on Early Childhood Developmental Milestones: A Retrospective Study

by Andrea D. Praticò, Manuela Lo Bianco, Roberta Leonardi, Agata Polizzi and Martino Ruggieri

Nutrients 2024, 16(24), 4395; https://doi.org/10.3390/nu16244395 - 20 Dec 2024

Cited by 1 | Viewed by 944

Abstract

Background: Vitamin D plays a pivotal role in early childhood development, influencing skeletal strength, neuromuscular coordination, and neurodevelopment. This study aimed to evaluate the impact of different durations of Vitamin D supplementation on achieving developmental milestones. Methods: A retrospective study was conducted on 209 children, divided into two cohorts based on Vitamin D supplementation duration: six months (n = 102) and twelve months (n = 107). Developmental milestones were assessed across motor (sitting, walking), fine motor (object tracking, grasping), and social (smiling, speech) domains. Statistical analyses, including t-tests and effect size calculations, were performed to compare the mean ages of milestone achievement. Results: The 12-month group achieved several milestones significantly earlier than the 6-month group. These included walking, object tracking, and combining words into phrases. Differences in other milestones, such as sitting and smiling, were not statistically significant. Effect sizes ranged from small to moderate. Conclusion: Extended Vitamin D supplementation is associated with modest yet significant advancements in key developmental milestones. However, socio-environmental factors, including parental involvement, likely contributed to these differences. This study’s retrospective design limits causal interpretation, emphasizing the need for prospective, randomized studies to validate findings. These results support the potential benefits of extending Vitamin D supplementation beyond six months to optimize developmental outcomes in infants. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

20 pages, 7249 KiB

Open AccessArticle

Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments

by Xin Wei, Dan Wang, Jiajia Liu, Qizhi Zhu, Ziming Xu, Jinzhe Niu and Weiping Xu

Nutrients 2024, 16(8), 1167; https://doi.org/10.3390/nu16081167 - 14 Apr 2024

Cited by 2 | Viewed by 1687

Abstract

Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, and in vitro experiments were integrated to verify the antidepressant active ingredients in PR and their mechanisms. A total of seven compounds in PR were found to be associated with 45 targets of depression. Preliminarily, DFV docking with cyclooxygenase 2 (COX2) showed good affinity. In vitro, DFV inhibited lipopolysaccharide (LPS)-induced inflammation of BV-2 cells, reversed amoeba-like morphological changes, and increased mitochondrial membrane potential. DFV reversed the malondialdehyde (MDA) overexpression and superoxide dismutase (SOD) expression inhibition in LPS-induced BV-2 cells and decreased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA expression levels in a dose-dependent manner. DFV inhibited both mRNA and protein expression levels of COX2 induced by LPS, and the activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and caspase1 was suppressed, thus exerting an antidepressant effect. This study proves that DFV may be an important component basis for PR to play an antidepressant role. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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19 pages, 4817 KiB

Open AccessArticle

Ellagic Acid Prevents α-Synuclein Spread and Mitigates Toxicity by Enhancing Autophagic Flux in an Animal Model of Parkinson’s Disease

by Nada Radwan, Engila Khan, Mustafa T. Ardah, Tohru Kitada and M. Emdadul Haque

Nutrients 2024, 16(1), 85; https://doi.org/10.3390/nu16010085 - 26 Dec 2023

Cited by 3 | Viewed by 2278

Abstract

Parkinson’s disease (PD) is the second most common neurological disorder, pathologically characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) as well as the formation of Lewy bodies composed mainly of α-synuclein (α-syn) aggregates. It has been documented that abnormal aggregation of α-syn is one of the major causes of developing PD. In the current study, administration of ellagic acid (EA), a polyphenolic compound (10 mg/kg bodyweight), significantly decreased α-syn spreading and preserved dopaminergic neurons in a male C57BL/6 mouse model of PD. Moreover, EA altered the autophagic flux, suggesting the involvement of a restorative mechanism meditated by EA treatment. Our data support that EA could play a major role in the clearing of toxic α-syn from spreading, in addition to the canonical antioxidative role, and thus preventing dopaminergic neuronal death. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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15 pages, 498 KiB

Open AccessArticle

Neurodevelopment and Dietary Intake in Toddlers—A Cross-Sectional Study from the Healthy Children 2021 Project

by Micaela Cunha-Rodrigues, Rafaela Rosário, Ana Duarte, Maria José Silva, Cláudia Augusto, Mónica Rodrigues, Patrícia Padrão and Pedro Moreira

Nutrients 2023, 15(24), 5105; https://doi.org/10.3390/nu15245105 - 14 Dec 2023

Cited by 3 | Viewed by 3776

Abstract

Little is known about the potential associations between neurodevelopment, dietary diversity and food processing in the toddler period. This study aimed to estimate the association between these dietary quality dimensions and neurodevelopment in toddlers. Data for this cross-sectional analysis came from the Healthy Children 2021 project and included 212 toddlers (51.9% females, aged 12–36 months) from 15 Portuguese childcare centers. Neurodevelopment was assessed through Bayley Scales of Infant and Toddler Development. Dietary intake was gathered by a two-day non-consecutive dietary recall. The food items were categorised with NOVA classification. Dietary diversity was explored through Minimum Dietary Diversity (MDD). Logistic regression models adjusted for potential confounders were performed. Girls with a higher energy contribution of unprocessed/minimally processed foods and with an above median MDD score had higher odds of achieving a higher neurodevelopment score (aOR:1.04; 95%CI 1.01; 1.08 and aOR:2.26; 95%CI 1.01; 5.06, respectively); no significant association was observed in boys. Our findings suggest that these dietary dimensions are associated with a higher neurodevelopment in toddler girls. This should be further studied as a possible early link between dietary factors and neurodevelopment. Promotion of healthy eating can be promising in improving neurocognitive development and might help to introduce public health recommendations for toddlers’ nutrition. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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15 pages, 1908 KiB

Open AccessArticle

Preventive Treatment with Astaxanthin Microencapsulated with Spirulina Powder, Administered in a Dose Range Equivalent to Human Consumption, Prevents LPS-Induced Cognitive Impairment in Rats

by Miquel Martin, Matteo M. Pusceddu, Joan Teichenné, Teresa Negra, Alan Connolly, Xavier Escoté, Helena Torrell Galceran, Adrià Cereto Massagué, Iris Samarra Mestre, Antoni del Pino Rius, Jordi Romero-Gimenez, Cristina Egea, Juan Maria Alcaide-Hidalgo and Josep Maria del Bas

Nutrients 2023, 15(13), 2854; https://doi.org/10.3390/nu15132854 - 23 Jun 2023

Cited by 2 | Viewed by 2490

Abstract

Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS. Alterations in memory processing were evaluated in the Y-Maze and Morris Water Maze (MWM) paradigms. Changes in microglia activation and in gut microbiota content were also investigated. Our results demonstrate that LPS modified long-term memory in the MWM and increased microglia activation in the hippocampus and prefrontal cortex. Preventive treatment with ASXSP ameliorated LPS-cognitive alterations and microglia activation in both brain regions. Moreover, ASXSP was able to partially revert LPS-induced gut dysbiosis. Our results demonstrate the neuroprotective benefits of ASX when microencapsulated with spirulina acting through different mechanisms, including antioxidant, anti-inflammatory and, probably, prebiotic actions. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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Review

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14 pages, 431 KiB

Open AccessReview

The Critical Role of Vitamin D Supplementation for Skeletal and Neurodevelopmental Outcomes in Preterm Neonates

by Roberta Leonardi, Carmine Mattia, Nunzia Decembrino, Agata Polizzi, Martino Ruggieri and Pasqua Betta

Nutrients 2025, 17(8), 1381; https://doi.org/10.3390/nu17081381 - 19 Apr 2025

Viewed by 300

Abstract

Background/Objectives: Metabolic bone disease of prematurity (MBDP) is a multifactorial disorder resulting from disrupted transplacental mineral transfer and postnatal nutritional deficits, particularly affecting preterm neonates born before 32 weeks of gestation or weighing under 1500 g. Although substantial research has focused on skeletal outcomes, few studies have explored the association between MBDP and neonatal neurological impairment. This narrative review is the first to integrate the pathophysiological mechanisms, diagnostic methods, and preventive strategies for MBDP, while simultaneously investigating its potential impact on neurodevelopment. Methods: A narrative review of recent peer-reviewed studies, systematic reviews, and clinical trials was performed focusing on biochemical markers (alkaline phosphatase, FGF23, calcium, and phosphorus), emerging tools such as bioelectrical impedance analysis (BIA), and the effects of early nutritional interventions on both skeletal and neurodevelopmental outcomes in preterm infants (n = seven included articles). Results: Early elevations in ALP, particularly when combined with low serum phosphorus and FGF23 levels, provide sensitive markers for identifying MBDP. Furthermore, insufficient vitamin D levels during gestation and in the neonatal period have been associated with increased risks of seizures, hypotonia, and developmental delays. Studies suggest that enhanced vitamin D supplementation in preterm infants (up to 800 IU/day) may improve mineral absorption and bone formation and confer neuroprotective benefits through anti-inflammatory and antioxidant mechanisms. Conclusions: This is the first review on the neurological implications of biochemical actors of MBDP. As a result, diagnostic and therapeutic strategies, including vitamin D supplementation, can improve bone and neurodevelopmental outcomes. Future prospective studies are required to standardize diagnostic criteria and optimize therapeutic regimens for enhanced long-term benefits. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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19 pages, 1955 KiB

Open AccessReview

The Potential Use of Honey as a Neuroprotective Agent for the Management of Neurodegenerative Diseases

by Mohammad Adi Mohammad Fadzil, Suraiami Mustar and Aswir Abd Rashed

Nutrients 2023, 15(7), 1558; https://doi.org/10.3390/nu15071558 - 23 Mar 2023

Cited by 10 | Viewed by 5943

Abstract

As the global population ages, there is an increasing research on managing neurodegenerative diseases that mainly affect the elderly. Honey is one of the natural products and functional foods widely studied for its neuroprotective properties. This review investigates honey’s effectiveness as a neuroprotective agent through in vitro, in vivo, and clinical research. The articles were browsed from three databases (PubMed, ScienceDirect, and Scopus) between the years of 2012 and 2022 using the keywords “honey” crossed with “neurodegenerative”. Out of the 16 articles, six in vitro, eight in vivo, one combination study, and one clinical intervention were compiled. Among the various types of honey studied, the Tualang and Thyme honey exhibited the highest antioxidant, anti-inflammatory, and anticholinesterase activity, leading to the prevention and management of multiple neurodegenerative diseases such as Alzheimer’s disease. The neuroprotective properties of honey are primarily attributed to its high polyphenol content, with quercetin and gallic acid being the most prominent. This review compiled considerable evidence of the anti-neurodegenerative properties of honey presented by in vitro and in vivo studies. However, more clinical intervention studies are required to support these findings further. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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Other

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24 pages, 2140 KiB

Open AccessSystematic Review

Bifidobacterium infantis and Bifidobacterium breve Improve Symptomatology and Neuronal Damage in Neurodegenerative Disease: A Systematic Review

by Manuel Reiriz, Ana Isabel Beltrán-Velasco, Víctor Echeverry-Alzate, Esther Martínez-Miguel, Silvia Gómez-Senent, Sara Uceda and Vicente Javier Clemente-Suárez

Nutrients 2025, 17(3), 391; https://doi.org/10.3390/nu17030391 - 22 Jan 2025

Cited by 1 | Viewed by 2999

Abstract

Background/Objectives: This systematic review focused on collecting the most significant findings on the impact of the administration of Bifidobacterium infantis (or Bifidobacterium longum subps. infantis) and Bifidobacterium breve, alone, in conjunction, or in combination with other strains, in the treatment of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). These diseases are characterized by the progressive degeneration of neurons, resulting in a broad spectrum of clinical manifestations. AD is typified by a progressive decline in cognitive abilities, while PD is marked by motor symptoms associated with the loss of dopamine (DA). Methods: Five different databases, ScienceDirect, Scopus, Wiley, PubMed, and Web of Science (WoS), were reviewed and the studies were screened for inclusion by the following criteria: (i) studies that specifically evaluated the use of Bifidobacterium infantis, Bifidobacterium longum subsp. infantis, or Bifidobacterium breve as a therapeutic intervention, either in human or animal models, in the context of neurodegenerative diseases; (ii) the studies were required to address one or more of the pathologies examined in this article, and the pathologies included, but were not limited to, neurodegeneration, Alzheimer’s disease, Parkinson’s disease, and oxidative stress; (iii) the full text was accessible online; and (iv) the article was written in English. Results: The data suggest that these probiotics have neuroprotective effects that may delay disease progression. Conclusions: This study provides updated insights into the use of these Bifidobacterium strains in neurodegenerative diseases like AD and PD, with the main limitation being the limited number of clinical trials available. Full article

(This article belongs to the Special Issue Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease)

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