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Functional Mechanism of B-Vitamins and Their Metabolites

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 126207

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Special Issue Editors

Dr. Elena Azzini

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Guest Editor

CREA—Research Centre for Food and Nutrition, Rome, Italy
Interests: food and nutrition; functional food; antioxidants; polyphenols; food biochemistry
Special Issues, Collections and Topics in MDPI journals

Dr. Stefania Ruggeri

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Council for Agricultural Research and Economics, Research Center for Food and Nutrition, 00178 Rome, Italy
Interests: nutritional status; maternal health; preconceptional health; population surveys; developmental age; food habits; food consumption; adherence to the Mediterranean diet; sedentary lifestyle; obesity prevention; children’s health; communication; community-based interventions
Special Issues, Collections and Topics in MDPI journals

Dr. Angela Polito

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Guest Editor

CREA—Research Centre for Food and Nutrition, 00178 Rome, Italy
Interests: nutritional status; energy metabolism; energy requirements; physical activity; body composition; obesity; anorexia nervosa; elderly
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dietary recommendations provide guidance on nutrient intakes that afford to fulfil requirements in a specified population. Traditionally, these recommendations were intended to prevent deficiency disorders, but today their aim is extended to the primary prevention of non-communicable diseases, improving the quality of total diet. The B vitamins include a group of eight water-soluble vitamins crucial for a wide range of several metabolic processes in the body. Most B vitamins are excreted quickly from the body with the only exceptions of vitamin B-12 and folate, which are stored in the liver, but folate deficiency is a highly-prevalent vitamin deficiency throughout the world, essentially due scarcity of vegetable food intake. The activity of these two vitamins is particularly crucial for cardiovascular, nervous and brain system function. With ageing the prevalence of age-related diseases and disabilities increases. The maintenance of an optimal nutritional status may contribute to health and wellbeing of the elderly as well as important for public health. Moreover, adequate folate intake is involved in the primary prevention of some congenital anomalies as neural tube and hearth birth defects.

A B-vitamin metabolite, homocysteine (tHcy) plays a key role in two metabolic pathways: remethylation and transsulforation. In the remethylation pathway homocysteine is remethylated to methionine, a reaction catalysed by methionine synthase, which uses vitamin B12 as co-factor and 5-methyltetrahydrofolate (5-MTHF) as a methyl donor. This remethylation takes place in most tissues including liver and kidneys. In the transsulfuration pathway, limited to liver and kidneys, homocysteine is irreversibly converted to cystathionine by cystathionine β-synthase, which requires vitamin B6 as a co-factor.

This Special Issue gives insight in the evolving field of the vitamin B group, as well as its metabolites, regarding mechanisms of action, deficiency, supplementation, health benefits, primary prevention, as well as assessment.

Dr. Elena Azzini
Dr. Stefania Ruggeri
Dr. Angela Polito
Guest Editors

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Keywords

dietary sources and bioavailability
preconceptional health promotion
elderly health
cardiovascular disease
frailty and impaired cognitive function

Published Papers (13 papers)

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Research

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22 pages, 2730 KiB

Open AccessArticle

The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD⁺ Level Is Lower than the Sirtuin-Saturating Concentrations

by Nae-Cherng Yang, Yu-Hung Cho and Inn Lee

Int. J. Mol. Sci. 2020, 21(1), 142; https://doi.org/10.3390/ijms21010142 - 24 Dec 2019

Cited by 8 | Viewed by 5442

Abstract

Calorie restriction can extend lifespan by increasing intracellular nicotinamide adenine dinucleotide (NAD⁺), thereby upregulating the activity of sirtuins (Caenorhabditis elegans Sir-2.1; human SIRT1). Nicotinic acid (NA) can be metabolized to NAD⁺; however, the calorie restriction mimetic (CRM) potential of NA is unclear. This study explored the ability and mechanism of NA to extend the lifespan of human Hs68 cells and C. elegans. We found that NA can efficiently increase the intracellular NAD⁺ levels in Hs68 cells and C. elegans; however, NA was only able to extend the lifespan of C. elegans. The steady-state NAD⁺ level in C. elegans was approximately 55 μM. When intracellular NAD⁺ was increased by a mutation of pme-1 (poly (ADP-ribose) metabolism enzyme 1) or by pretreatment with NAD⁺ in the medium, the lifespan extension ability of NA disappeared. Additionally, the saturating concentration of NAD⁺ required by SIRT1 was approximately 200 μM; however, the steady-state concentration of NAD⁺ in Hs68 cells reached up to 460 μM. These results demonstrate that the lifespan extension ability of NA depends on whether the intracellular level of NAD⁺ is lower than the sirtuin-saturating concentration in Hs68 cells and in C. elegans. Thus, the CRM potential of NA should be limited to individuals with lower intracellular NAD⁺. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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14 pages, 2988 KiB

Open AccessArticle

Brain Susceptibility to Methyl Donor Deficiency: From Fetal Programming to Aging Outcome in Rats

by Ziad Hassan, David Coelho, Tunay Kokten, Jean-Marc Alberto, Rémy Umoret, Jean-Luc Daval, Jean-Louis Guéant, Carine Bossenmeyer-Pourié and Grégory Pourié

Int. J. Mol. Sci. 2019, 20(22), 5692; https://doi.org/10.3390/ijms20225692 - 14 Nov 2019

Cited by 11 | Viewed by 2303

Abstract

Deficiencies in methyl donors, folate, and vitamin B12 are known to lead to brain function defects. Fetal development is the most studied but data are also available for such an impact in elderly rats. To compare the functional consequences of nutritional deficiency in young versus adult rats, we monitored behavioral outcomes of cerebellum and hippocampus circuits in the offspring of deficient mother rats and in adult rats fed a deficient diet from 2 to 8 months-of-age. We present data showing that the main deleterious consequences are found in young ages compared to adult ones, in terms of movement coordination and learning abilities. Moreover, we obtained sex and age differences in the deleterious effects on these functions and on neuronal layer integrity in growing young rats, while deficient adults presented only slight functional alterations without tissue damage. Actually, the cerebellum and the hippocampus develop and maturate according to different time lap windows and we demonstrate that a switch to a normal diet can only rescue circuits that present a long permissive window of time, such as the cerebellum, whereas the hippocampus does not. Thus, we argue, as others have, for supplements or fortifications given over a longer time than the developmental period. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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13 pages, 3317 KiB

Open AccessArticle

Methyl Donor Deficiency during Gestation and Lactation in the Rat Affects the Expression of Neuropeptides and Related Receptors in the Hypothalamus

by Lynda Saber Cherif, Grégory Pourié, Andréa Geoffroy, Amélia Julien, Déborah Helle, Aurélie Robert, Rémy Umoret, Jean-Louis Guéant, Carine Bossenmeyer-Pourié and Jean-Luc Daval

Int. J. Mol. Sci. 2019, 20(20), 5097; https://doi.org/10.3390/ijms20205097 - 14 Oct 2019

Cited by 11 | Viewed by 2660

Abstract

The micronutrients vitamins B9 and B12 act as methyl donors in the one-carbon metabolism involved in transmethylation reactions which critically influence epigenetic mechanisms and gene expression. Both vitamins are essential for proper development, and their deficiency during pregnancy has been associated with a wide range of disorders, including persisting growth retardation. Energy homeostasis and feeding are centrally regulated by the hypothalamus which integrates peripheral signals and acts through several orexigenic and anorexigenic mediators. We studied this regulating system in a rat model of methyl donor deficiency during gestation and lactation. At weaning, a predominance of the anorexigenic pathway was observed in deficient pups, with increased plasma peptide YY and increased hypothalamic pro-opiomelanocortin (POMC) mRNA, in line with abnormal leptin, ghrelin, and insulin secretion and/or signaling during critical periods of fetal and/or postnatal development of the hypothalamus. These results suggest that early methyl donor deficiency can affect the development and function of energy balance circuits, resulting in growth and weight deficits. Maternal administration of folic acid (3 mg/kg/day) during the perinatal period tended to rectify peripheral metabolic signaling and central neuropeptide and receptor expression, leading to reduced growth retardation. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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11 pages, 2541 KiB

Open AccessArticle

Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice

by Hee Jae Lee and Soo Jin Yang

Int. J. Mol. Sci. 2019, 20(17), 4196; https://doi.org/10.3390/ijms20174196 - 27 Aug 2019

Cited by 35 | Viewed by 5360

Abstract

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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18 pages, 2076 KiB

Open AccessArticle

Anti-Tumor Effects of Vitamin B2, B6 and B9 in Promonocytic Lymphoma Cells

by Kathleen Mikkelsen, Monica D. Prakash, Nyanbol Kuol, Kulmira Nurgali, Lily Stojanovska and Vasso Apostolopoulos

Int. J. Mol. Sci. 2019, 20(15), 3763; https://doi.org/10.3390/ijms20153763 - 01 Aug 2019

Cited by 38 | Viewed by 6227

Abstract

Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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14 pages, 3501 KiB

Open AccessArticle

Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid

by Andréa Geoffroy, Lynda Saber-Cherif, Grégory Pourié, Déborah Helle, Rémy Umoret, Jean-Louis Guéant, Carine Bossenmeyer-Pourié and Jean-Luc Daval

Int. J. Mol. Sci. 2019, 20(4), 973; https://doi.org/10.3390/ijms20040973 - 23 Feb 2019

Cited by 19 | Viewed by 3494

Abstract

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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14 pages, 1709 KiB

Open AccessArticle

NAD Metabolome Analysis in Human Cells Using ¹H NMR Spectroscopy

by Konstantin Shabalin, Kirill Nerinovski, Alexander Yakimov, Veronika Kulikova, Maria Svetlova, Ljudmila Solovjeva, Mikhail Khodorkovskiy, Stepan Gambaryan, Richard Cunningham, Marie E. Migaud, Mathias Ziegler and Andrey Nikiforov

Int. J. Mol. Sci. 2018, 19(12), 3906; https://doi.org/10.3390/ijms19123906 - 06 Dec 2018

Cited by 24 | Viewed by 6968

Abstract

Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form, NADP, are the major coenzymes of redox reactions in central metabolic pathways. Nicotinamide adenine dinucleotide is also used to generate second messengers, such as cyclic ADP-ribose, and serves as substrate for protein modifications including ADP-ribosylation and protein deacetylation by sirtuins. The regulation of these metabolic and signaling processes depends on NAD availability. Generally, human cells accomplish their NAD supply through biosynthesis using different forms of vitamin B3: Nicotinamide (Nam) and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR). These precursors are converted to the corresponding mononucleotides NMN and NAMN, which are adenylylated to the dinucleotides NAD and NAAD, respectively. Here, we have developed an NMR-based experimental approach to detect and quantify NAD(P) and its biosynthetic intermediates in human cell extracts. Using this method, we have determined NAD, NADP, NMN and Nam pools in HEK293 cells cultivated in standard culture medium containing Nam as the only NAD precursor. When cells were grown in the additional presence of both NAR and NR, intracellular pools of deamidated NAD intermediates (NAR, NAMN and NAAD) were also detectable. We have also tested this method to quantify NAD+ in human platelets and erythrocytes. Our results demonstrate that ¹H NMR spectroscopy provides a powerful method for the assessment of the cellular NAD metabolome. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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Review

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27 pages, 4053 KiB

Open AccessReview

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

by Elena Azzini, Stefania Ruggeri and Angela Polito

Int. J. Mol. Sci. 2020, 21(4), 1421; https://doi.org/10.3390/ijms21041421 - 20 Feb 2020

Cited by 71 | Viewed by 16110

Abstract

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case–control experimental designs and the study of interactions between different factors it should be emphasized. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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41 pages, 869 KiB

Open AccessReview

B Vitamins and Fatty Acids: What Do They Share with Small Vessel Disease-Related Dementia?

by Rita Moretti and Costanza Peinkhofer

Int. J. Mol. Sci. 2019, 20(22), 5797; https://doi.org/10.3390/ijms20225797 - 18 Nov 2019

Cited by 31 | Viewed by 8162

Abstract

Many studies have been written on vitamin supplementation, fatty acid, and dementia, but results are still under debate, and no definite conclusion has yet been drawn. Nevertheless, a significant amount of lab evidence confirms that vitamins of the B group are tightly related to gene control for endothelium protection, act as antioxidants, play a co-enzymatic role in the most critical biochemical reactions inside the brain, and cooperate with many other elements, such as choline, for the synthesis of polyunsaturated phosphatidylcholine, through S-adenosyl-methionine (SAM) methyl donation. B-vitamins have anti-inflammatory properties and act in protective roles against neurodegenerative mechanisms, for example, through modulation of the glutamate currents and a reduction of the calcium currents. In addition, they also have extraordinary antioxidant properties. However, laboratory data are far from clinical practice. Many studies have tried to apply these results in everyday clinical activity, but results have been discouraging and far from a possible resolution of the associated mysteries, like those represented by Alzheimer’s disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria—MCI or AD? Which diagnostic criteria should be applied for small vessel disease-related dementia? In addition, no general schema exists for determining a possible correct time of implementation to have effective results. Here we present an up-to-date review of the literature on such topics, shedding some light on the possible interaction of vitamins and phosphatidylcholine, and their role in brain metabolism and catabolism. Further studies should take into account all of these questions, with well-designed and world-homogeneous trials. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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30 pages, 5312 KiB

Open AccessReview

Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications

by Daniel Fernández-Villa, Maria Rosa Aguilar and Luis Rojo

Int. J. Mol. Sci. 2019, 20(20), 4996; https://doi.org/10.3390/ijms20204996 - 09 Oct 2019

Cited by 98 | Viewed by 17079

Abstract

Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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26 pages, 1593 KiB

Open AccessReview

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications

by Valeria Gasperi, Matteo Sibilano, Isabella Savini and Maria Valeria Catani

Int. J. Mol. Sci. 2019, 20(4), 974; https://doi.org/10.3390/ijms20040974 - 23 Feb 2019

Cited by 129 | Viewed by 30395

Abstract

Niacin (also known as “vitamin B₃” or “vitamin PP”) includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B₃ has long been recognized as a key mediator of neuronal development and survival. Here, we will overview available literature data on the neuroprotective role of niacin and its derivatives, especially focusing especially on its involvement in neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s diseases), as well as in other neuropathological conditions (ischemic and traumatic injuries, headache and psychiatric disorders). Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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21 pages, 1292 KiB

Open AccessReview

The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice

by Rita Moretti and Paola Caruso

Int. J. Mol. Sci. 2019, 20(1), 231; https://doi.org/10.3390/ijms20010231 - 08 Jan 2019

Cited by 151 | Viewed by 13732

Abstract

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke. The aim of our research is to review the possible role of HHcy in neurodegenerative disease and stroke and to understand its pathogenesis. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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22 pages, 1869 KiB

Open AccessReview

Tissue Engineering Therapies Based on Folic Acid and Other Vitamin B Derivatives. Functional Mechanisms and Current Applications in Regenerative Medicine

by Daniel Fernández-Villa, Mirta Jiménez Gómez-Lavín, Cristina Abradelo, Julio San Román and Luis Rojo

Int. J. Mol. Sci. 2018, 19(12), 4068; https://doi.org/10.3390/ijms19124068 - 16 Dec 2018

Cited by 28 | Viewed by 6418

Abstract

B-vitamins are a group of soluble vitamins which are cofactors of some of the enzymes involved in the metabolic pathways of carbohydrates, fats and proteins. These compounds participate in a number of functions as cardiovascular, brain or nervous systems. Folic acid is described as an accessible and multifunctional niche component that can be used safely, even combined with other compounds, which gives it high versatility. Also, due to its non-toxicity and great stability, folic acid has attracted much attention from researchers in the biomedical and bioengineering area, with an increasing number of works directed at using folic acid and its derivatives in tissue engineering therapies as well as regenerative medicine. Thus, this review provides an updated discussion about the most relevant advances achieved during the last five years, where folic acid and other vitamins B have been used as key bioactive compounds for enhancing the effectiveness of biomaterials’ performance and biological functions for the regeneration of tissues and organs. Full article

(This article belongs to the Special Issue Functional Mechanism of B-Vitamins and Their Metabolites)

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