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Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and...
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Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications

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

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 21009

Special Issue Editors

Dr. Mercedes Camacho Pérez de Madrid

E-Mail Website
Guest Editor
Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau – Centre CERCA, Barcelona, Spain
Interests: inflammatory mechanisms involves in cardiovascular diseases; eicosanoids in the cardiovascular context; biomarkers for early diagnosis of cardiovascular diseases; mechanisms underlying the development of aortic abdominal aneurysm (AAA); correlation between biochemical and structural alterations of the aortic wall and the clinical parameters of patients with AAA; analysis of genes regulated by hypoxia/ischemia; neovascularization
Special Issues, Collections and Topics in MDPI journals
Dr. Josep Julve

E-Mail Website
Guest Editor
1. Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau–Centre CERCA, Barcelona, Spain
2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
Interests: obesity; diabetes; lipoprotein metabolism; metabolic syndrome; therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Beyond the well-established role of nicotinamide adenine dinucleotide (NAD)+ in redox reactions, NAD+ has been widely reported to influence the activity of a wide range of regulatory proteins that require NAD+ as an essential cosubstrate to perform their function. NAD+-dependent histone deacetylases, also defined as sirtuins, polyADP-ribose polymerases, and cyclic ADP-ribose synthases are recognized as their main representatives and mediate multiple key cellular processes, such as DNA repair, mitochondrial function, metabolic homeostasis, apoptosis and cell survival, inflammation, and lifespan.

NAD+ metabolism is negatively influenced by aging, and tissue NAD+ content is altered in a broad spectrum of pathological conditions, including metabolic diseases and muscular and neurological disorders. Conversely, increased NAD+ levels have been shown to be beneficial in the course of many diseases and have become a topic of renewed interest in recent years, notably focused on demonstrating the beneficial preventive and/or therapeutical effects of boosting cellular NAD+ metabolism in different disease models.

The potential of dietary precursors of NAD+ (i.e., nicotinic acid, nicotinamide, nicotinamide mononucleotide, and nicotinamide riboside), collectively referred to as vitamin B3 derivatives, in manipulating NAD+ concentrations has demonstrated multiple beneficial effects in a large spectrum of diseases in animal models. However, the translation of these favorable effects into clinical benefits is now becoming one of the main exciting challenges to improve health span and lifespan in humans.

This Special Issue will encourage preclinical and clinical research focused on the potential of dietary NAD+ raising strategies to manage chronic metabolic/inflammatory diseases and age-related health issues.

Dr. Mercedes Camacho Pérez de Madrid
Dr. Josep Julve
Guest Editors

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

  • vitamin B3
  • NAD+
  • inflammation
  • metabolism
  • aging

Published Papers (6 papers)

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Editorial

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4 pages, 227 KiB  
Editorial
NAD+ Precursors: A Physiological Reboot?
by Julia Niño-Narvión, Mercedes Camacho and Josep Julve
Nutrients 2023, 15(20), 4479; https://doi.org/10.3390/nu15204479 - 23 Oct 2023
Viewed by 1661
Abstract
In this Editorial, we comment on a series of recent articles featured in the Special Issue “Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications” in Nutrients [...] Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)

Research

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15 pages, 4819 KiB  
Article
Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms
by Jeimy Katherine Torres-Méndez, Julia Niño-Narvión, Patricia Martinez-Santos, Elena María Goretti Diarte-Añazco, Karen Alejandra Méndez-Lara, Tania Vázquez del Olmo, Noemi Rotllan, Maria Teresa Julián, Núria Alonso, Didac Mauricio, Mercedes Camacho, Juan Pablo Muñoz, Joana Rossell and Josep Julve
Nutrients 2023, 15(14), 3083; https://doi.org/10.3390/nu15143083 - 9 Jul 2023
Cited by 3 | Viewed by 1862
Abstract
This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i.p.) streptozotocin (STZ) [...] Read more.
This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i.p.) streptozotocin (STZ) injections. Diabetic mice were randomly distributed in different experimental groups and challenged to different doses of NAM (untreated, NAM low-dose, LD, 0.1%; NAM high-dose, HD, 0.25%) for 25 days. A control, non-diabetic group of mice was used as a reference. The NAD+ content was increased in the brains of NAM-treated mice compared with untreated diabetic mice (NAM LD: 3-fold; NAM HD: 3-fold, p-value < 0.05). Immunohistochemical staining revealed that markers of inflammation (TNFα: NAM LD: −35%; NAM HD: −46%; p-value < 0.05) and microglial activation (IBA-1: NAM LD: −29%; NAM HD: −50%; p-value < 0.05; BDKRB1: NAM LD: −36%; NAM HD: −37%; p-value < 0.05) in brains from NAM-treated diabetic mice were significantly decreased compared with non-treated T1D mice. This finding was accompanied by a concomitant alleviation of nuclear NFκB (p65) signaling in treated diabetic mice (NFκB (p65): NAM LD: −38%; NAM HD: −53%, p-value < 0.05). Notably, the acetylated form of the nuclear NFκB (p65) was significantly decreased in the brains of NAM-treated, diabetic mice (NAM LD: −48%; NAM HD: −63%, p-value < 0.05) and inversely correlated with NAD+ content (r = −0.50, p-value = 0.03), suggesting increased activity of NAD+-dependent deacetylases in the brains of treated mice. Thus, dietary NAM supplementation in diabetic T1D mice prevented brain inflammation via NAD+-dependent deacetylation mechanisms, suggesting an increased action of sirtuin signaling. Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)
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16 pages, 3788 KiB  
Article
Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD+ by Generating Dihydronicotinamide Riboside
by Eleonora Ciarlo, Magali Joffraud, Faisal Hayat, Maria Pilar Giner, Judith Giroud-Gerbetant, Jose Luis Sanchez-Garcia, Marie Rumpler, Sofia Moco, Marie E. Migaud and Carles Cantó
Nutrients 2022, 14(13), 2752; https://doi.org/10.3390/nu14132752 - 1 Jul 2022
Cited by 10 | Viewed by 3884
Abstract
Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD+), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly [...] Read more.
Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD+), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD+ precursors influence intracellular NAD+ levels. We identified dihydronicotinic acid riboside (NARH) as a new NAD+ precursor in hepatic cells. Second, we demonstrate how NARH, but not any other NAD+ precursor, can act synergistically with nicotinamide riboside (NR) to increase NAD+ levels in cultured cells and in mice. Finally, we demonstrate that the large increase in NAD+ prompted by the combination of these two precursors is due to their chemical interaction and conversion to dihydronicotinamide riboside (NRH). Altogether, this work demonstrates for the first time that NARH can act as a NAD+ precursor in mammalian cells and how different NAD+ precursors can interact and influence each other when co-administered. Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)
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15 pages, 1558 KiB  
Article
Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood
by Alba Serrano, Andreu Palou, M. Luisa Bonet and Joan Ribot
Nutrients 2022, 14(11), 2259; https://doi.org/10.3390/nu14112259 - 28 May 2022
Cited by 4 | Viewed by 2223
Abstract
Nicotinamide riboside, an NAD+ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD+ decline in tissues. The metabolic programming activity of NR supplementation in [...] Read more.
Nicotinamide riboside, an NAD+ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD+ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation. Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)
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Review

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24 pages, 1212 KiB  
Review
NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota
by Julia Niño-Narvión, Marina Idalia Rojo-López, Patricia Martinez-Santos, Joana Rossell, Antonio J. Ruiz-Alcaraz, Núria Alonso, Bruno Ramos-Molina, Didac Mauricio and Josep Julve
Nutrients 2023, 15(13), 2992; https://doi.org/10.3390/nu15132992 - 30 Jun 2023
Cited by 4 | Viewed by 3334
Abstract
The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as well as a coenzyme for different NAD+-consuming enzymes involved in the physiological homeostasis of different organs [...] Read more.
The oxidized form of nicotinamide adenine dinucleotide (NAD+) is a critical metabolite for living cells. NAD+ may act either as a cofactor for many cellular reactions as well as a coenzyme for different NAD+-consuming enzymes involved in the physiological homeostasis of different organs and systems. In mammals, NAD+ is synthesized from either tryptophan or other vitamin B3 intermediates that act as NAD+ precursors. Recent research suggests that NAD+ precursors play a crucial role in maintaining the integrity of the gut barrier. Indeed, its deficiency has been associated with enhanced gut inflammation and leakage, and dysbiosis. Conversely, NAD+-increasing therapies may confer protection against intestinal inflammation in experimental conditions and human patients, with accumulating evidence indicating that such favorable effects could be, at least in part, mediated by concomitant changes in the composition of intestinal microbiota. However, the mechanisms by which NAD+-based treatments affect the microbiota are still poorly understood. In this context, we have focused specifically on the impact of NAD+ deficiency on intestinal inflammation and dysbiosis in animal and human models. We have further explored the relationship between NAD+ and improved host intestinal metabolism and immunity and the composition of microbiota in vivo. Overall, this comprehensive review aims to provide a new perspective on the effect of NAD+-increasing strategies on host intestinal physiology. Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)
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15 pages, 1267 KiB  
Review
Emerging Role of Nicotinamide Riboside in Health and Diseases
by Chiranjeev Sharma, Dickson Donu and Yana Cen
Nutrients 2022, 14(19), 3889; https://doi.org/10.3390/nu14193889 - 20 Sep 2022
Cited by 9 | Viewed by 6831
Abstract
Among all the NAD+ precursors, nicotinamide riboside (NR) has gained the most attention as a potent NAD+-enhancement agent. This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans. Boosting intracellular NAD+ [...] Read more.
Among all the NAD+ precursors, nicotinamide riboside (NR) has gained the most attention as a potent NAD+-enhancement agent. This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans. Boosting intracellular NAD+ concentrations using NR has been shown to provide protective effects against a broad spectrum of pathological conditions, such as neurodegenerative diseases, diabetes, and hearing loss. In this review, an integrated overview of NR research will be presented. The role NR plays in the NAD+ biosynthetic pathway will be introduced, followed by a discussion on the synthesis of NR using chemical and enzymatic approaches. NR’s effects on regulating normal physiology and pathophysiology will also be presented, focusing on the studies published in the last five years. Full article
(This article belongs to the Special Issue Emerging Benefits of Vitamin B3 Derivatives on Aging, Health and Disease: From Basic Research to Translational Applications)
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