Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.

Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome.

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.

The potential prophylactic and therapeutic impacts of niacin on ischemia/reperfusion injury of testis.

INTRODUCTION: The testicular ischemia-reperfusion (I/R) injury is characterized by the excessive aggregation of un-scavenged reactive oxygen species, leading to the heightened levels of oxidative stress. This phenomenon plays a pivotal role in the pathophysiology of testicular torsion damage. OBJECTIVE: The current study aimed to detect the prophylactic and therapeutic effects of niacin on testicular I/R injury. STUDY DESIGN: Twenty-four healthy adult male Sprague Dawley rats were randomly allocated into three groups as follows: (1) sham group, (2) torsion/detorsion (T/D) group, and (3) treatment group which received 200 mg/kg niacin along with testicular T/D. Torsion/detorsion was induced by 2 h of torsion followed by 10 days of reperfusion period. In the treatment group, niacin was injected 30 min before the reperfusion period intraperitoneally and continued for 10 days by oral gavage. RESULTS: T/D was associated with marked decreases in terms of sperm count, viability, and kinematic parameters versus the sham group (P < 0.05), which niacin significantly reverted the kinematic parameters (P < 0.05). I/R injury caused a significant increase in the number of abnormal epididymal sperms compared to the sham group (P < 0.05). Niacin decreased the epididymal sperm abnormality significantly compared to the T/D group (P < 0.05). Tissue abnormalities in T/D group, such as edema, hyperemia, inflammation, and necrosis were completely visible histopathologically, while the histological changes in the niacin-treated group were better than those in the T/D group. Regarding the pathological parametric evaluations, I/R injury significantly reduced the mean testicular biopsy score (MTBS), germinal epithelial cell thickness (GECT), and mean seminiferous tubular diameter (MSTD), and increased the tubular hypoplasia/atrophy (THA) compared to the sham group (P < 0.05), which niacin treatment significantly improved the MTBS and GECT compared to the T/D group (P < 0.05). T/D significantly increased the oxidative stress index (OSI) and lipid peroxidation (MDA) (P < 0.05). Niacin significantly reduced the OSI and MDA levels compared to the T/D group (P < 0.05). DISCUSSION: The current study found that niacin has preventive/therapeutic effects against the elevation of oxidative stress markers and depletion of antioxidants during I/R injury. Following administration of niacin, a reduction in histologic injury was observed in rats. In our study, we showed the antioxidant properties of niacin and its capacity to protect against I/R damage. CONCLUSION: The findings of the present investigation revealed that niacin, as an antioxidant agent, can suppress the oxidative stress induced by testicular I/R injury, and can be used as a supplementary agent in the treatment of those undergoing testicular torsion surgery.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

BACKGROUND: This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. METHODS: The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. RESULTS: A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. CONCLUSION: The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. HIGHLIGHTS: • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

Altered HCAR3 expression may underlying the blunted niacin responses of the psychiatric disorders and the risk of schizophrenia.

AIM: Blunted niacin response (BNR) was an endophenotype of schizophrenia, but the underlying mechanism remains unclarified. The objective of this study was to verify whether genes associated with BNR pathway constitute the genetic basis and the pathological mechanism of BNR phenotypic psychiatric patients. METHODS: Two independent sample sets consisting of 971 subjects were enrolled in this study. A total of 62 variants were genotyped in the discovery set, then the related variants were verified in the verification set. The published PGC GWAS data were used to validate the associations between the variants and psychiatry disorders. RT-PCR analysis, eQTL data, and Dual-Luciferase Reporter experiment were used to investigate the potential molecular mechanisms of the variants underlying BNR. RESULTS: The results showed that two SNPs, rs56959712 in HCAR2 and rs2454721 in HCAR3 were significantly associated with niacin response. The risk allele T of rs2454721 could affect the niacin responses of psychiatric patients through elevated HCAR3 gene expression. These two genes, especially HCAR3, were significantly associated with the risk of schizophrenia, as identified in this study and verified using the published GWAS data. CONCLUSION: HCAR3 is a novel schizophrenia susceptibility gene which is significantly associated with blunted niacin response in schizophrenia. In-depth investigation of HCAR3 is of great significance for uncovering the pathogenesis and propose new therapeutic targets for psychiatric disorders, especially for the BNR subgroup patients.

Nicotinic acid modulates microglial TREM-2 gene in Phytohaemagglutinin-Induced in vitro model of Alzheimer's disease like pathology.

Alzheimer's disease (AD) is a multifactorial,neurodegenerative disorder linked withextracellular amyloid beta (Aß) plaques deposition and formation of intracellular neurofibrillary tangles (NFTs). Currently, no effective therapies are available to cure AD. Neuroinflammation isa well-known hallmark in the onset and advancement of AD and triggering receptor expressed on myeloid cells-2 (TREM-2), a microglial gene, is responsible for regulating inflammatory responses and clearance of cellular debris. Loss of TREM-2functionincreases neuroinflammation associated expression of pro-inflammatory markersthus resultingin reduced clearance of Aß that further aid in disease progression.Therefore, targeting neuroinflammation is a good therapeutic approach for AD. This study aimed to determine the neuroprotective effect of nicotinic acid (NA) in vitro model of AD-like pathology induced in F-98 cell line using Phytohemagglutinin (PHA). MTT assay was employed for checking the cell viability as well as the proliferation of the cells following treatment with NA. PHA at the concentration of 10 µg/mL produces maximum plaques. The neuroprotective effect of NA was next evaluated against PHA-induced plaques and it was observed that NA reverses the damages induced by PHA i.e., by inhibiting the clustering of the cells and replacing the damaged cells with the new ones. Further, NA also increased the expression of TREM-2/DAP-12 with parallel decreased in the expression of IL-1ß, TNF-α and iNOS. It also successfully altered disease associated ADAM-10 and BACE-1 compared to PHA control. These findings suggest that NA might be considered as a good therapeutic candidate for the treatment of neurodegenerative disorders like AD.

Niacin treatment prevents bone loss in iron overload osteoporotic rats via activation of SIRT1 signaling pathway.

Recently, more and more studies have revealed that iron overload can lead to osteoporosis by inducing oxidative stress. Niacin (NAN), also known as nicotinate or vitamin B3, has been confirmed to possess potent antioxidative effects. In addition, very little is currently known about the protective effects of NAN on iron overload in osteoporotic bone tissue. Therefore, we aimed to evaluate the protective effect of niacin on iron overload-induced bone injury and to investigate the effect and underlying mechanisms of the niacin and iron overload on intracellular antioxidant properties. When MC3T3-E1 and RAW264.7 cells were cultured in the presence of ammonium ferric citrate(FAC), NAN therapy could increase the matrix mineralization and promote expression of osteogenic markers in MC3T3-E1, inhibit osteoclastic differentiation of RAW264.7 cells, while increasing intracellular reactive oxygen species (ROS) levels and strengthening mitochondrial membrane potential (MMP). In the ovariectomized (OVX) rat model, NAN had an obvious protective effect against iron-overloaded injury. Meanwhile, superoxide dismutase 2 (SOD2), intracellular antioxidant enzymes and silent information regulator type 1 (SIRT1), were up-regulated in response to NAN exposures in MC3T3-E1. Furthermore, SIRT1 inhibitor EX527 attenuated the protective effects of NAN. Results revealed that NAN could stimulate osteogenic differentiation, inhibit osteoclastic differentiation and markedly increased antioxidant properties in cells through the induction of SIRT1. Studies suggest that niacin is a promising agent for preventing bone loss in iron overload conditions.

A Second Look at Niacin.

Niacin is the third vitamin to be discovered and, therefore. is known as vitamin B3. It has a long history of medicinal use-nutritionally and as a skin tone brightening agent in skin care. Recent studies have suggested that niacin could be useful as an adjunctive treatment for coronavirus disease 2019 (COVID-19) and mitigating the damaging effect of blue light to the skin. Niacin, also known as nicotinic acid, nicotinamide, and niacinamide, is a physiologically active form of vitamin B3. Medicinal benefits of niacin were observed in 1902, when for the first time, patients with pellagra were treated with yeast that contained vitamin B3. Niacin has a variety of uses, particularly in treating various skin conditions, including topically as an anti-acne treatment, promoting epidermal sphingolipid synthesis, moderating photoimmunosuppression, and reducing hyperpigmentation. Niacinamide could be beneficial as an adjunctive treatment for COVID-19 and for decreasing stress if the skin is excessively exposed to blue light.

Anti-Inflammatory, Antioxidant and Neuroprotective Effects of Niacin on Mild Traumatic Brain Injury in Rats.

AIM: To study the effects of niacin, a water-soluble vitamin, on inflammation, oxidative stress and apoptotic processes observed after mild traumatic brain injury (TBI). MATERIAL AND METHODS: A total of 25 Wistar albino male rats were randomly divided into control (n=9), TBI + Placebo group (n=9), TBI + niacin (500 mg/kg; n=7) groups. Mild TBI was performed under anesthesia by dropping a 300 g weight from a height of 1 meter onto the skull. Behavioral tests were applied before and 24 hours after TBI. Luminol and lucigenin levels and tissue cytokine levels were measured. Histopathological damage was scored in brain tissue. RESULTS: After mild TBI, luminol and lucigenin levels were increased (p < 0.001), and their levels were decreased with niacin treatment (p < 0.01-p < 0.001). An increased score was obtained with trauma in the tail suspension test (p < 0.01), showing depressive behavior. The number of entries to arms in Y-maze test were decreased in TBI group compared to pre-traumatic values (p < 0.01), while discrimination (p < 0.05) and recognition indices (p < 0.05) in object recognition test were decreased with trauma, but niacin treatment did not change the outcomes in behavioral tests. Levels of the anti-inflammatory cytokine IL-10 were decreased with trauma, and increased with niacin treatment (p < 0.05). The histological damage score was increased with trauma (p < 0.001), and decreased with niacin treatment in the cortex (p < 0.05), and hippocampal dentate gyrus region (p < 0.01). CONCLUSION: Niacin treatment after mild TBI inhibited trauma-induced production of reactive oxygen derivatives and elevated the anti-inflammatory IL-10 level. Niacin treatment ameliorated the histopathologically evident damage.

Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects.

Background The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) in patients with heart failure through unknown mechanisms. 3-OHB activates the hydroxycarboxylic acid receptor 2 (HCA2), which increases prostaglandins and suppresses circulating free fatty acids. We investigated whether the cardiovascular effects of 3-OHB involved HCA2 activation and if the potent HCA2-stimulator niacin may increase CO. Methods and Results Twelve patients with heart failure with reduced ejection fraction were included in a randomized crossover study and examined by right heart catheterization, echocardiography, and blood sampling on 2 separate days. On study day 1, patients received aspirin to block the HCA2 downstream cyclooxygenase enzyme, followed by 3-OHB and placebo infusions in random order. We compared the results with those of a previous study in which patients received no aspirin. On study day 2, patients received niacin and placebo. The primary end point was CO. 3-OHB increased CO (2.3 L/min, P<0.01), stroke volume (19 mL, P<0.01), heart rate (10 bpm, P<0.01), and mixed venous saturation (5%, P<0.01) with preceding aspirin. 3-OHB did not change prostaglandin levels, neither in the ketone/placebo group receiving aspirin nor the previous study cohort. Aspirin did not block 3-OHB-induced changes in CO (P=0.43). 3-OHB decreased free fatty acids by 58% (P=0.01). Niacin increased prostaglandin D2 levels by 330% (P<0.02) and reduced free fatty acids by 75% (P<0.01) but did not affect CO. Conclusions The acute increase in CO during 3-OHB infusion was not modified by aspirin, and niacin had no hemodynamic effects. These findings show that HCA2 receptor-mediated effects were not involved in the hemodynamic response to 3-OHB. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04703361.

NAD+ repletion with niacin counteracts cancer cachexia.

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.

The Promise of Niacin in Neurology.

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.

A Systematic Review of Cost-Effectiveness of Non-Statin Lipid-Lowering Drugs for Primary and Secondary Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

Although studies of nonstatin lipid-lowering therapies have demonstrated cardiovascular benefits; whether these benefits provide good value has not been evaluated in type 2 diabetes mellitus patients. A systematic review was performed to include studies on the cost-effectiveness of non-statin lipid-lowering therapies in type 2 diabetes mellitus patients with/without cardiovascular disease. Thirteen studies were included; ezetimibe (n = 8), proprotein convertase subtilisin/kexin type 9 inhibitors (n = 4), fenofibrate (n = 2), nicotinic acid (n = 1), extended-release niacin/laropiprant (n = 1), and icosapent ethyl (n = 1). Six studies considered ezetimibe + statin to be a cost-effective compared to statins monotherapy, three studies suggested that proprotein convertase subtilisin/kexin type 9inhibitors + statins were not cost-effective compared to statin + ezetimibe. Fenofibrate was a cost-effective either as monotherapy or combined with a statin compared to statin or fenofibrate monotherapy. Nicotinic acid and proprotein convertase subtilisin/kexin type 9 compared to statin monotherapy were also cost-effective. Icosapent ethyl was cost-effective compared to standard care but not using the wholesale acquisition cost.

Pellagra in Zanzibar: a rare diagnosis.

BACKGROUND: Pellagra is a nutritional disease resulting from a deficiency of vitamin B3 (niacin) primarily due to corn consumption, especially in developing countries, but in developed countries, it can occur secondarily as a consequence of chronic alcoholism, malabsorption, certain drugs, and bariatric surgery. RESULTS: We present a case of a 32-year-old woman from a rural area in Zanzibar who was a heavy alcohol consumer and came in with features suggestive of pellagra. CONCLUSION: Our therapeutic approach consisted of niacin 500 mg once daily and betamethasone + salicylic acid ointment twice a day until lesions resolved and showed noticeable improvement.

Association between niacin and mortality among patients with cancer in the NHANES retrospective cohort.

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.

Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01178320.

Niacin mitigates blood-brain barrier tight junctional proteins dysregulation and cerebral inflammation in ketamine rat model of psychosis: Role of GPR109A receptor.

Dysregulated inflammatory responses and blood-brain barrier (BBB) dysfunction are recognized as central factors in the development of psychiatric disorders. The present study was designed to evaluate the effect of niacin on BBB integrity in ketamine-induced model of psychosis. Meanwhile, mepenzolate bromide (MPN), a GPR109A receptor blocker, was used to investigate the role of this receptor on the observed niacin's effect. Male Wistar rats received ketamine (30 mg/kg/day, i.p) for 5 consecutive days and then niacin (40 mg/kg/day, p.o), with or without MPN (5 mg/kg/day, i.p), was given for the subsequent 15 days. Three days before the end of experiment, rats were behaviorally tested using open field, novel object recognition, social interaction, and forced swimming tests. Niacin significantly ameliorated ketamine-induced behavioral deficits, amended gamma aminobutyric acid and glutamate concentration, decreased tumor necrosis factor-α and matrix metallopeptidase 9 levels, and increased netrin-1 contents in the hippocampus of rats. Niacin also augmented the hippocampal expression of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the BBB integrity. Moreover, the histopathologic changes in hippocampal neurons were alleviated. Since all the beneficial effects of niacin in the present investigation were partially abolished by the co-administration of MPN; GPR109A receptor was proven to partially mediate the observed antipsychotic effects of niacin. These data revealed that GPR109A-mediated signaling pathways might represent potential targets for therapeutic interventions to prevent or slow the progression of psychosis.

Clinical analysis of alcoholic pellagra: A single-center retrospective study.

BACKGROUND: Pellagra caused by niacin deficiency in alcoholics can be easily misdiagnosed because of similar symptoms to other alcohol-related diseases and the lack of the classical triad of signs. AIM: This study aimed to define the clinical presentation of alcoholic pellagra for early diagnosis and timely treatment. METHODS: The clinical data of 16 alcohol-dependent patients who had pellagra and treated in our hospital from January 2002 to December 2019 were retrospectively analyzed. The local medical ethics committee approval (Medical Ethics Committee of Affiliated Hospital of XuZhou Medical University, XYFY2020-KL247-02) for this study has been obtained. RESULTS: The main complaints of the 16 patients were skin lesions (six cases), diarrhea (six cases), and mental disorders (four cases). Then, 13 cases had typical skin lesions, and 3 patients had a full spectrum of diarrhea, dementia, and dermatitis (3D). In terms of the main diagnosis, 2 patients had pellagra and Wernicke's encephalopathy, 3 patients had pellagra and alcohol-withdrawal syndrome, and the other patients had pellagra. After sufficient amounts of niacin and multivitamin B were given, clinical symptoms improved rapidly, and no sequelae were observed during follow-up. CONCLUSIONS: Pellagra is rarely manifested as a full 3D spectrum, with only one or two characteristics, which lack diagnostic specificity, especially in individuals with alcoholism. Physicians should maintain a high degree of suspicion of niacin deficiency in alcoholics. Alcohol-dependent patients with pellagra may be accompanied by complications of Wernicke's encephalopathy and alcohol-withdrawal syndrome. Prompt identification and timely treatment with a sufficient amount of niacin in combination with other vitamins and a certain amount of Zn can achieve a good prognosis of pellagra.