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Neurotherapeutics : the Journal of the... Jul 2023Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence... (Review)
Review
Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.
Topics: Humans; Niacin; Amyloid beta-Peptides; Pellagra; Nervous System Diseases; Alzheimer Disease; Neurology
PubMed: 37084148
DOI: 10.1007/s13311-023-01376-2 -
International Journal of Molecular... Feb 2019Niacin (also known as "vitamin B₃" or "vitamin PP") includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine... (Review)
Review
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).
Topics: Animals; Central Nervous System; Clinical Trials as Topic; Humans; Nervous System Diseases; Niacin
PubMed: 30813414
DOI: 10.3390/ijms20040974 -
BMC Cancer Nov 2022The vitamin niacin is used as a lipid-regulating supplement, but it is unknown whether niacin has a positive influence on cancer prognosis. In this study, we examine the...
BACKGROUND
The vitamin niacin is used as a lipid-regulating supplement, but it is unknown whether niacin has a positive influence on cancer prognosis. In this study, we examine the relationship between niacin intake and mortality among patients with cancer.
METHODS
Our study utilized all available continuous data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Multivariable Cox regression models were applied in order to investigate dietary niacin intake's association with mortality. We compared the survival probability between groups of low and high niacin intake by plotting Kaplan-Meier curves. An analysis of subgroups was used to investigate heterogeneity sources.
RESULTS
A total of 3504 participants were included in the cohort, with 1054 deaths. One thousand eight hundred forty-seven participants (52.3%) were female, 2548 participants (73.4%) were white, and the mean age (SE) was 65.38 years (0.32). According to multivariate logistic regression analysis, niacin intake was negatively associated with mortality outcomes in patients with cancer, with P values below 0.05 in all models. In subgroup analyses based on sex, age, and BMI, the association persisted. The Kaplan-Meier curves indicate that high niacin intake groups have better survival rates than low intake groups. Niacin supplementation improved cancer mortality but not all-cause mortality.
CONCLUSION
According to our study, higher dietary niacin intake was associated with lower mortality in cancer patients. Niacin supplements improved cancer survival rates, but not all causes of mortality.
Topics: Humans; Female; Aged; Male; Niacin; Nutrition Surveys; Retrospective Studies; Vitamins; Diet; Neoplasms
PubMed: 36376861
DOI: 10.1186/s12885-022-10265-4 -
Briefings in Bioinformatics Mar 2021Patients with colorectal cancer (CRC) may be susceptible to the coronavirus disease-2019 (COVID-19). However, anti-CRC/COVID-19 treatment options are currently...
OBJECTIVES
Patients with colorectal cancer (CRC) may be susceptible to the coronavirus disease-2019 (COVID-19). However, anti-CRC/COVID-19 treatment options are currently unavailable. Since niacin is a vitamin with cytoprotective and anti-inflammatory functions, this study aimed to evaluate the possible functional roles and underlying mechanisms of action of niacin as an anti-COVID-19 and -CRC therapy.
INTERVENTIONS
We used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of niacin in CRC/COVID-19.
MEASUREMENTS AND MAIN RESULTS
We revealed the clinical characteristics of CRC patients and COVID-19 patients, including predisposing genes, survival rate and prognosis. Moreover, the results of molecular docking analysis indicated that niacin exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions and signaling pathways of niacin in CRC/COVID-19. The analysis indicated that niacin could help in treating CRC/COVID-19 through cytoprotection, enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of cellular microenvironment. Furthermore, five core pharmacological targets of niacin in CRC/COVID-19 were also identified, including BCL2L1, PTGS2, IL1B, IFNG and SERPINE1.
CONCLUSIONS
This study, for the first time, revealed the niacin-associated molecular functions and pharmacological targets for treating CRC/COVID-19, as COVID-19 remains a serious pandemic. But the findings were not validated in actual CRC patients infected with COVID-19, so further investigation is needed to confirm the potential use of niacin for treating CRC/COVID-19.
Topics: Aged; COVID-19; Colorectal Neoplasms; Computational Biology; Female; Humans; Male; Middle Aged; Molecular Docking Simulation; Niacin; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33169132
DOI: 10.1093/bib/bbaa300 -
Nature Communications Apr 2023Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism...
Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD and downregulation of Nrk2, an NAD biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD repletion therapy in cachectic mice reveals that NAD precursor, vitamin B3 niacin, efficiently corrects tissue NAD levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD in the pathophysiology of human cancer cachexia. Overall, our results propose NAD metabolism as a therapy target for cachectic cancer patients.
Topics: Humans; Mice; Animals; Niacin; NAD; Cachexia; Niacinamide; Neoplasms; Muscle, Skeletal
PubMed: 37012289
DOI: 10.1038/s41467-023-37595-6 -
Advances in Nutrition (Bethesda, Md.) May 2016
Topics: Female; Humans; Maternal Nutritional Physiological Phenomena; Niacin; Pregnancy; Randomized Controlled Trials as Topic; Recommended Dietary Allowances
PubMed: 27184282
DOI: 10.3945/an.115.011239 -
Nutrients Dec 2020Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding... (Review)
Review
Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.
Topics: Animals; Butyrates; Dietary Supplements; Dysbiosis; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Niacin; Parkinson Disease; Permeability
PubMed: 33374784
DOI: 10.3390/nu13010028 -
The American Journal of Managed Care Sep 2002Niacin is an important therapeutic option for the treatment of dyslipidemias and is the only agent currently available that favorably affects all components of the lipid... (Review)
Review
Niacin is an important therapeutic option for the treatment of dyslipidemias and is the only agent currently available that favorably affects all components of the lipid profile to a significant degree. Niacin has consistently been shown to significantly reduce levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein (a), while having the greatest high-density lipoprotein (HDL) cholesterol-raising effects of all available agents. Niacin has also been shown to significantly reduce coronary events and total mortality. Niacin is available in 3 formulations: immediate-release (IR), sustained-release (SR), and a newer formulation, niacin extended-release (ER), all of which differ in their pharmacokinetic, efficacy, and safety profiles. Conventional niacin therapy has notable limitations that include flushing, most often seen with IR formulations, and hepatotoxicity, associated with SR formulations. These side effects are related to the absorption rate and subsequent metabolism of niacin as delivered from the different products. Niacin ER has a delivery system allowing absorption rates intermediate to that of niacin IR and SR. As a result, niacin ER achieves the efficacy of niacin IR with a reduced incidence of flushing and without the hepatic effects seen with niacin SR. The pharmacist should be familiar with the differences among and the advantages and disadvantages of each formulation to educate patients and help them achieve the optimal therapeutic benefit of niacin while minimizing adverse effects.
Topics: Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Hyperlipidemias; Hypolipidemic Agents; Niacin; Pharmacists; Professional Role; United States
PubMed: 12240702
DOI: No ID Found -
Cell Reports Nov 2023Niacin, an age-old lipid-lowering drug, acts through the hydroxycarboxylic acid receptor 2 (HCAR2), a G-protein-coupled receptor (GPCR). Yet, its use is hindered by side...
Niacin, an age-old lipid-lowering drug, acts through the hydroxycarboxylic acid receptor 2 (HCAR2), a G-protein-coupled receptor (GPCR). Yet, its use is hindered by side effects like skin flushing. To address this, specific HCAR2 agonists, like MK-6892 and GSK256073, with fewer adverse effects have been created. However, the activation mechanism of HCAR2 by niacin and these new agonists is not well understood. Here, we present three cryoelectron microscopy structures of Gi-coupled HCAR2 bound to niacin, MK-6892, and GSK256073. Our findings show that different ligands induce varying binding pockets in HCAR2, influenced by aromatic amino acid clusters (W91, H161, W188, H189, and F193) from receptors ECL1, TM4, and TM5. Additionally, conserved residues R111 and Y284, unique to the HCA receptor family, likely initiate activation signal propagation in HCAR2. This study provides insights into ligand recognition, receptor activation, and G protein coupling mediated by HCAR2, laying the groundwork for developing HCAR2-targeted drugs.
Topics: Humans; Niacin; Cryoelectron Microscopy; Cyclohexanecarboxylic Acids; Receptors, G-Protein-Coupled; Ligands; Lipids
PubMed: 37952153
DOI: 10.1016/j.celrep.2023.113406 -
Nutrients Oct 2023In 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:...
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 [...].
Topics: NAD; Niacinamide; Niacin
PubMed: 37892554
DOI: 10.3390/nu15204479