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Abstract Background Cardiovascular disease (CVD) poses a significant challenge to global public health. Dietary intervention therapy offers high cost-effectiveness for treating CVD. Currently, there is limited research on the dietary niacin intake and survival of CVD patients. This study aims to examine the association of dietary niacin intake with long-term survival in people with CVD. Methods A nationally representative sample of 4,377 diabetes subjects was drawn from the NHANES (National Health and Nutrition Examination Survey) data collected between 2003 and 2018. Dietary niacin intake in this study represents either the average of the two recalls or the value from one recall (if only one recall was available for a participant). Weighted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs to examine the associations between dietary niacin intake and the risk of all-cause and CVD mortality. Results After adjustment for multiple covariates, HRs and 95% CIs in model 3 indicated that participants in the highest quartile (Quartile 4) of dietary niacin intake were at lower risk for all-cause mortality (HR = 0.74, 95% CI: 0.60–0.90, P for trend = 0.010) and CVD mortality (HR = 0.67, 95% CI:0.51–0.89, P for trend = 0.020). Conclusion Higher dietary niacin intake may be associated with a reduced risk of all-cause and cardiovascular disease mortality among CVD patients. Additionally, significant interactions were found between dietary niacin intake and BMI as well as vitamin B12 subgroups.

Abstract Aim This study aims to explore the relationship between niacin intake and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) within a large, multi-ethnic cohort. Methods A total of 2946 participants from the National Health and Nutrition Examination Survey (NHANES) were carefully selected based on strict inclusion and exclusion criteria. Participants meeting the eligibility criteria underwent two dietary recall interviews, and niacin intake was calculated using the USDA’s Food and Nutrient Database for Dietary Studies (FNDDS). Liver steatosis was diagnosed using a Controlled Attenuation Parameter (CAP) of 248 dB/m, and MASLD diagnosis was based on metabolic indicators. Weighted multivariate logistic regression was utilized to analyze the correlation between niacin intake and MASLD prevalence, with potential nonlinear relationships explored through restricted cubic spline (RCS) regression. Results Analysis of baseline data revealed that MASLD patients had lower niacin intake levels and poorer metabolic biomarker profiles. Both RCS analysis and multivariate logistic regression indicated a U-shaped association between niacin intake and MASLD prevalence. Specifically, there was a non-linear dose-response relationship, with the odds of MASLD gradually decreasing with increasing niacin intake until reaching a threshold of 23.6 mg, beyond which the odds of MASLD began to increase. Conclusion This study confirms a U-shaped nonlinear relationship between niacin intake and MASLD prevalence within the diverse American population.

Abstract Background NAXE‐encephalopathy or early‐onset progressive encephalopathy with brain edema and/or leukoencephalopathy‐1 (PEBEL‐1) and NAXD‐encephalopathy (PEBEL‐2) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures with the onset being usually within the first three years of life. It usually leads to rapid disease progression and death in early childhood. Anecdotal reports suggest that niacin, through its role in nicotinamide adenine dinucleotinde (NAD) de novo synthesis, corrects biochemical derangement, and slows down disease progression. Reports so far have supported this observation. Methods We describe a patient with a confirmed PEBEL‐1 diagnosis and report his clinical response to niacin therapy. Moreover, we systematically searched the literature for PEBEL‐1 and PEBEL‐2 patients treated with niacin and details about response to treatment and clinical data were reviewed. Furthermore, we are describing off‐label use of a COX2 inhibitor to treat niacin‐related urticaria in NAXE‐encephalopathy. Results So far, seven patients with PEBEL‐1 and PEBEL‐2 treated with niacin were reported, and all patients showed a good response for therapy or stabilization of symptoms. We report a patient exhibiting PEBEL‐1 with an unfavorable outcome despite showing initial stabilization and receiving the highest dose of niacin reported to date. Niacin therapy failed to halt disease progression or attain stabilization of the disease in this patient. Conclusion Despite previous positive results for niacin supplementation in patients with PEBEL‐1 and PEBEL‐2, this is the first report of a patient with PEBEL‐1 who deteriorated to fatal outcome despite being started on the highest dose of niacin therapy reported to date.

Abstract Background There are contradictory effects regarding the effect of NAD + precursor on glucose metabolism and liver enzymes. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD + precursor supplementation on glucose metabolism, C-reactive protein (CRP), and liver enzymes. Methods PubMed/MEDLINE, Web of Science, SCOPUS, and Embase databases were searched using standard keywords to identify all controlled trials investigating the glucose metabolism, CRP, and liver enzymes effects of NAD + precursor. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes. Results Forty-five articles with 9256 participants’ were included in this article. The pooled findings showed that NAD + precursor supplementation had a significant increase in glucose (WMD: 2.17 mg/dL, 95% CI: 0.68, 3.66, P = 0.004) and HbA1c (WMD: 0.11, 95% CI: 0.06, 0.16, P

The pathogenesis of osteoporosis is driven by several mechanisms including the imbalance between osteoblastic bone formation and osteoclastic bone resorption. Currently, the role of Niacin (NA), also known as vitamin B3, in the regulation of osteoblastic differentiation is not fully understood. Data from the NHANES database were employed to investigate the association of NA intake with the prevalence of osteoporosis. Alterations in mRNA and protein levels of genes and proteins involved in osteogenic differentiation were evaluated via techniques including qRT-PCR, protein immunoblotting, Alkaline Phosphatase (ALP) activity analysis, ALP staining, and Alizarin Red staining. Changes in the mouse skeletal system were investigated by organizational analysis and Micro-CT. The results indicated that NA promoted osteogenic differentiation. Co-immunoprecipitation and chromatin immunoprecipitation were performed to explore the underlying mechanisms. It was observed that NA promoted AREG expression by deacetylating C/EBPβ via SIRT2, thereby activating the PI3K-AKT signaling pathway. It also enhanced the activity of the pivotal glycolytic enzyme, PFKFB3. This cascade amplified osteoblast glycolysis, facilitating osteoblast differentiation. These findings demonstrate that NA modulates glucose metabolism and influences osteogenic differentiation via the SIRT2-C/EBPβ-AREG pathway, suggesting that NA may be a potential therapeutic agent for the management of osteoporosis, and AREG could be a plausible target.

BackgroundA recent study has shown that niacin supplementation induces the conversion of type II to type I muscle fibres, thereby promoting a phenotypic shift in oxidative metabolism in porcine skeletal muscle. These effects may be mediated by modulation of the AMPK1/SIRT1 pathway, which activates peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key regulator of fibre conversion, thereby promoting skeletal muscle mitochondrial biogenesis and myofibre conversion. In this study, we explored how niacin (NA) supplementation impacts the quality of meat and the characteristics of muscle fibers in Taihe Black-bone Silky Fowls (TBsf) exposed to heat conditions.MethodsChickens were rationally assigned to five different treatment groups with five replicates of six chickens each: thermophilic (TN), heat stress (HS) and HS + NA (HN) groups, with the HN group being supplemented with 200, 400 and 800 mg/kg (HS + NA0.02, HS + NA0.04 and HS + NA0.08) NA in the premix, respectively.ResultsThe results of the experiment showed that addition of 800 mg/kg NA to the diet significantly improved TBsf muscle tenderness compared to HS. Dietary enrichment with 200-800 mg/kg NA significantly increased total antioxidant capacity, superoxide dismutase, and glutathione peroxidase activities, while significantly decreasing malondialdehyde compared to HS. Incorporation of 200-800 mg/kg NA into the diet significantly reduced lactate dehydrogenase activity and myosin heavy chain (MyHC-IIB) gene expression. Furthermore, adding 800 mg/kg NA can significantly enhance the mRNA expression of mitochondrial transcription factors (TFAM and TFB1M) in TBsf skeletal muscle. Adding 400 and 800 mg/kg of NA significantly increased the mRNA expression of AMP-activated protein kinase 1 (AMPK1), PGC-1α, cytochrome c oxidase (Cytc), and nuclear respiratory factor (NRF-1) in the skeletal muscle of TBsf. Supplementing NA at 200-400 mg/kg significantly increased the expression of Sirtuin 1 (SIRT1) mRNA in TBsf skeletal muscle.ConclusionThe experimental results showed that the addition of NA to the diet reduced the shear force of TBsf muscle under heat exposure conditions. It increased the proportion of type I muscle fibres by increasing the antioxidant capacity of the muscle and by promoting mitochondr fibreial biogenesis. Considering the results of this study, it is recommended that TBsf be supplemented with 400-800 mg/kg of NA in the diet to reduce the adverse effects of heat stress on meat quality.

ObjectiveThe relationship between dietary niacin intake (DNI) and mortality rates among patients afflicted with chronic kidney disease (CKD) is a subject of debate. Utilizing data derived from the National Health and Nutrition Examination Survey (NHANES), this study adopts a retrospective cohort design with an aim to investigate the association in the American adult patients with CKD.MethodsA cohort study was conducted in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 that enrolled 6,191 CKD patients aged 20 years and above. We collected data on mortality through 31 December 2018. DNI was measured using a 24-h recall method. The relationship between DNI levels and mortality from all causes and cardiovascular causes was analyzed using weighted Cox proportional hazards models. The Kaplan–Meier (K-M) survival curve was plotted to illustrate these associations.ResultsFollowing a median monitoring period of 85 months, it was observed that 2,419 individuals (33.08%) succumbed to all causes, whereas cardiovascular-related deaths were recorded for 746 participants (10.45%). When controlling for confounders, an inverse relationship was established between DNI and mortality rates. Specifically, a marginal increase of 1 mg/day in DNI corresponded to a reduced Hazard Ratios (HRs) of 0.993 (0.987, 0.999; p = 0.027) for all-cause mortality and 0.980 (0.969, 0.991; p

ObjectiveThis investigation aims to elucidate the correlations between dietary intakes of vitamin E, B6, and niacin and the incidence of cataracts, utilizing the comprehensive NHANES 2005–2008 dataset to affirm the prophylactic roles of these nutrients against cataract formation.MethodsUsing data from the NHANES 2005–2008 cycles, this analysis concentrated on 7,247 subjects after exclusion based on incomplete dietary or cataract data. The identification of cataracts was determined through participants’ self-reported ophthalmic surgical history. Nutritional intake was gauged using the automated multiple pass method, and the data were analyzed using logistic and quantile regression analyses to investigate the relationship between vitamin consumption and cataract prevalence.ResultsOur analysis identified significant inverse associations between the intake of vitamins E, B6, and niacin and the risk of cataract development. Specifically, higher intakes of vitamin B6 (OR = 0.85, 95% CI = 0.76–0.96, p = 0.0073) and niacin (OR = 0.98, 95% CI = 0.97–1.00, p = 0.0067) in the top quartile were significantly associated with a reduced likelihood of cataract occurrence. Vitamin E intake showed a consistent reduction in cataract risk across different intake levels (OR = 0.96, 95% CI = 0.94–0.99, p = 0.0087), demonstrating a nonlinear inverse correlation.ConclusionThe outcomes indicate that elevated consumption of vitamin B6 and niacin, in conjunction with regular vitamin E intake, may have the potential to delay or prevent cataract genesis. These results suggest a novel nutritional strategy for cataract prevention and management, advocating that focused nutrient supplementation could be instrumental in preserving eye health and reducing the risk of cataracts. Further research is recommended to validate these findings and establish optimal dosages for maximum benefit.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and involves various pathogenic mechanisms, including oxidative stress and neuroinflammation. Niacin, an important cofactor in mitochondrial energy metabolism, may play a key role in the pathogenesis of PD. An in-depth exploration of the relationship between niacin and mitochondrial energy metabolism may provide new targets for the treatment of PD. The present study was designed to examine the association between dietary niacin intake and the risk of PD in US adults. Data from adults aged 40 years and older collected during cycles of the United States (US) National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were used. A multiple logistic regression model was used to analyze the relationship between dietary niacin intake and the risk of PD. Further linear tests using restricted cubic splines (RCS) were performed to explore the shape of the dose–response relationship. Subgroup stratification and interaction analyses were conducted according to years of education, marital status, smoking, and hypertension to evaluate the stability of the association between different subgroups. A total of 20,211 participants were included in this study, of which 192 were diagnosed with PD. In the fully adjusted multiple logistic regression model, dietary niacin intake was negatively associated with the risk of PD (OR: 0.77, 95%CI: 0.6–0.99; p = 0.042). In the RCS linear test, the occurrence of PD was negatively correlated with dietary niacin intake (nonlinearity: p = 0.232). In stratified analyses, dietary niacin intake was more strongly associated with PD and acted as an important protective factor in patients with fewer years of education (OR: 0.35, 95%CI: 0.13–0.93), married or cohabitating (OR: 0.71, 95%CI: 0.5–0.99), taking dietary supplements (OR: 0.6, 95%CI: 0.37 0.97), non-smokers (OR: 0.57, 95%CI: 0.39–0.85), those with hypertension (OR: 0.63, 95%CI: 0.63–0.95), coronary artery disease (OR: 0.77, 95%CI: 0.6–1), and stroke (OR: 0.75, 95%CI: 0.88–0.98), but the interaction was not statistically significant in all subgroups. Dietary niacin intake was inversely associated with PD risk in US adults, with a 23% reduction in risk for each 10 mg increase in niacin intake.

ObjectiveThis study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population.MethodsA stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA’s Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression.ResultsA comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations.ConclusionThis investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.

A ten-week feeding trial was conducted to investigate the effect of dietary niacin on intestinal health of juvenile turbot. Three isonitrogenous and isolipidic experimental diets were formulated, containing 0 (NA0, as control), 20 (NA20), and 80 (NA80) mg/kg niacin, respectively. Compared with the NA0 group, dietary 20 mg/kg niacin significantly reduced the gene expression of NF-κB and pro-inflammatory cytokines (TNF-α, IFN-γ and IL-8), and increased the expression of TGF-β. Furthermore, dietary niacin at 20 mg/kg significantly decreased the gene expression of Caspase-9 and tumor suppressor p53, and increased the ratio of Bcl-2/Bax. Sequencing of intestinal bacterial 16 S rRNA V4 region revealed that dietary 20 mg/kg niacin significantly up-regulated the abundance of lactic acid bacteria (Lactobacillus, Streptococcus, Lactococcus, Leuconostoc and Enterococcus) and Anoxybacillus, and optimized the composition of intestinal bacterial community. However, diet NA80 increased the relative abundance of opportunistic pathogen Vibrio and Pseudomonas. Collectively, dietary niacin at 20 mg/kg is beneficial to gut health of juvenile turbot, however, excessive addition of niacin (80 mg/kg) showed negative effect on intestinal microbial communities.

Modern agriculture seeks, through technology, to increase agricultural productivity, aiming at greater sustainability during food production. The application of vitamins meets this objective, acting as a biostimulant for different cultivation conditions. In this sense, the aim of this research is to evaluate the effect of the foliar application of nicotinamide on the soybean crop in two growing environments. The treatments were composed of the nicotinamide concentrations of 0, 100, 200, 300, 400, 500, and 600 mg L−1 of water applied when the plants were at the R3 stage (beginning of pod formation), exogenously, by foliar spraying. The application of nicotinamide resulted in increases in the vegetative traits of plant height and the number of branches per plant by 9.7 and 7.8%, respectively. Regarding the productive characteristics, considering the average of the two cultivation sites, the application of the vitamin resulted in increments of about 15.62, 18.57, 20.53, 4.32, and 19.19% on the number of pods, number of grains, mass of grains per plant, mass of 1,000 grains, and yield, respectively. In this way, we conclude that nicotinamide, applied at concentrations ranging from 237.8 to 373.8 mg L−1, promotes benefits to soybean growth and yield in different environments, and can be considered as a biostimulant.

Niacin is the precursor to pyridine nucleotides NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). Niacin (vitamin B3) is the common term for nicotinic acid, nicotinamide and derivatives that exhibit the biological activity of nicotinamide. Furthermore, the indispensable amino acid tryptophan is the substrate for de novo synthesis of NAD. Thus, the requirements and intake of niacin are expressed as niacin equivalents (NE).The focus of interest for niacin over the last decade has primarily been on pharmacological doses of nicotinic acid as a lipid-lowering agent and other NAD precursors as potential enhancers of cellular NAD+ concentrations. None of these studies, however, makes a useful contribution to understanding dietary requirements in healthy populations.The requirement for niacin is estimated based on the relationship between intake and biochemical indices of niacin status, primarily urinary excretion of nicotinamide metabolites.

ABSTRACT: Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood β-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB

Fermented seeds and their bioactive compounds have captivated global interest due to their functional properties. Basil seeds are used worldwide in the food, cosmetic, and pharmaceutical industries, but their functional and nutritional properties after fermentation are not known. The aim of this study was to optimize the effect of fermentation on the improvement in the functional properties of basil seeds by Lactobacillus plantarum. Basil seed samples were categorized into seven water volumes (named A–G) and fermented for 24, 48, 72, and 96 h with L. Plantarum. The results show that the pH and total microbial content (TMC) significantly changed after 24 h of fermentation (p < 0.05). Fermentation significantly increased the antioxidant properties and niacin content of basil seeds compared with non-fermented control samples (p < 0.05). Fermented samples G-24, G-48, and G-72 (samples with a ratio of 1 g (basil):10 mL (water) fermented for 24,48 and 72 h), exhibited the highest DPPH and ABTS• scavenging activity. The total polyphenol content (TPC) was most prominent in the samples G-72, G-24, and G-48, respectively. Sample G-48 showed the highest antioxidant activity. Notably, sample G-24 showed a significant increase in niacin content (64 µg/mL). These results underscore that varying moisture levels and fermentation durations have a significant impact on the nutritional/functional value of basil seeds. Overall, fermenting basil seeds with L. plantarum increased their functional properties with greater antioxidant and TPC activities as well as increased nutritional value.

A conventional questionnaire-based assessment of acetic acid intake is based on the intake of seasonings such as mayonnaise, which could thereby lead to an underestimation. We here determine the relationships of acetic acid intake with nutrient intake estimated using a food recording app (Asken) based on meal recipes. A total of 141 individuals (48 men and 93 women) used the app for at least 7 days per month. The mean daily intake of acetic acid was 0.16 ± 0.19 g and the mean frequency of acetic acid intake was 2.77 ± 1.66 days per week. A multivariate regression analysis adjusted for age, sex, BMI, and energy intake revealed that the amount of acetic acid consumed was significantly and positively associated with the intake of protein (11.9 (5.1, 18.6), p < 0.001), cholesterol (80.7 (4.5, 156.9), p = 0.04), and all vitamins except vitamin K. The frequency of acetic acid intake was significantly and positively associated with protein (1.04 (0.20, 1.87), p = 0.015), vitamin B1 (0.3 (0.02,0.5), p = 0.031), niacin (0.5 (0.04,1.0), p = 0.032), and vitamin B12 (0.4 (0.1,0.7), p = 0.002) intake, suggesting that individuals who frequently consume acetic acid tend to consume more protein and some vitamins. Thus, the amount and frequency of acetic acid may reflect protein and vitamin intake.

Abstract 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.

IntroductionNiacin is one of the essential vitamins for mammals. It plays important roles in maintaining rumen microecological homeostasis. Our previous study indicated that dietary niacin significantly elevated intramuscular fat content (IMF) in castrated finishing steers. Whether niacin affects fat deposition by regulating the microbial composition and functional capacities of gastrointestinal microbiome has been unknown yet.MethodsIn this study, 16 castrated Xiangzhong Black cattle were randomly assigned into either control group fed with a basal concentrate diet (n = 8) or niacin group fed with a basal concentrate diet added 1000 mg/kg niacin (n = 8). Seven rumen samples and five cecum content samples were randomly collected from each of control and niacin groups for metagenomic sequencing analysis.ResultsA total of 2,981,786 non-redundant microbial genes were obtained from all tested samples. Based on this, the phylogenetic compositions of the rumen and cecum microbiome were characterized. We found that bacteria dominated the rumen and cecum microbiome. Prevotella ruminicola and Ruminococcus flavefaciens were the most abundant bacterial species in the rumen microbiome, while Clostridiales bacterium and Eubacterium rectale were predominant bacterial species in the cecum microbiome. Rumen microbiome had significantly higher abundances of GHs, GTs, and PLs, while cecum microbiome was enriched by CBMs and AAs. We found a significant effect of dietary niacin on rumen microbiome, but not on cecum microbiome. Dietary niacin up-regulated the abundances of bacterial species producing lactic acid and butyrate, fermenting lactic acid, and participating in lipid hydrolysis, and degradation and assimilation of nitrogen-containing compounds, but down-regulated the abundances of several pathogens and bacterial species involved in the metabolism of proteins and peptides, and methane emissions. From the correlation analysis, we suggested that niacin improved nutrient digestion and absorption, but reduced energy loss, and Valine, leucine and isoleucine degradation of rumen microbiome, which resulted in the increased host IMF.ConclusionThe results suggested that dietary manipulation, such as the supplementation of niacin, should be regarded as the effective and convenient way to improve IMF of castrated finishing steers by regulating rumen microbiome.

Abstract Background Although dietary intake is believed to be associated with constipation, there is currently a lack of research exploring the relationship between niacin intake and constipation. Therefore, the aim of this study is to investigate the association between niacin intake in adults and constipation using data from the National Health and Nutrition Examination Survey (NHANES). Methods This study included 5170 participants (aged ≥ 20 years) from the NHANES survey conducted between 2009 and 2010. Participants who reported experiencing constipation “always”, “most of the time”, or “sometimes” in the past 12 months were defined as constipation cases. The daily niacin intake was obtained from dietary recall and dietary supplement recalls of the patients. Weighted multivariate logistic regression analysis, restricted cubic spline regression, subgroup analysis, and interaction analysis were used to assess the correlation between niacin intake and constipation. Results After adjustment for covariates, the multivariate logistic regression model showed that low niacin intake was associated with a higher risk of constipation (Model 1: OR: 0.917, 95% CI 0.854–0.985, P = 0.023; Model 2: OR: 0.871, 95% CI 0.794–0.955, P = 0.01). After dividing niacin intake into four groups, a daily intake of 0–18 mg niacin was associated with a higher risk of constipation (Model 1: OR: 1.059, 95% CI 1.012–1.106, P = 0.019; Model 2: OR: 1.073, 95% CI 1.025–1.123, P = 0.013). The restricted cubic spline regression analysis also showed a non-linear relationship between niacin intake and the risk of constipation. Conclusion The findings of this study suggested that daily intake of 0–18 mg of niacin was associated with a higher risk of constipation compared to a daily intake of 18–27 mg of niacin.

Abstract Background Previous studies have shown that an antioxidant diet is a protective factor against depression. However, the association between niacin, an important antioxidant consumed from the diet, and depression has received little attention. Therefore, we explored the association between niacin intake and depression through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Methods Depression was measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Niacin intake was assessed through 24-h dietary recall interviews. The relationship of niacin intake with depression among adults in US was assessed by using a weighted multiple logistic regression model with subgroup analysis. Non-linear associations were explored using restricted cubic spline models. And we used a two-piece-wise logistic regression model with smoothing to explore the threshold for association between them. Results A total of 16,098 adults were included in this study. Compared with individuals with lowest niacin intake Q1 (≤ 15.96 mg/day), the adjusted OR values for dietary niacin intake and depression in Q2 (15.97–22.86 mg/day), Q3 (22.87–32.28 mg/day) and Q4 (≥ 32.29 mg/day), were 0.92 (95% CI: 0.70–1.20), 0.76 (95% CI: 0.56–0.99,) and 0.68 (95% CI: 0.48–0.98), respectively. The results were not modified by sex, by age and by BMI. Furthermore, the relationship between dietary niacin intake and depression exhibited a U-shaped curve (nonlinear, p

BackgroundEarly-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL-1) is an autosomal recessive disorder whereby a fluctuating clinical course is exacerbated by febrile illnesses. Pathogenic NAD(P)HX epimerase (NAXE) gene mutations underpin this disorder. This mutation damages the metabolite repair system involved in regenerating crucial redox carriers. Longer survival has rarely been reported in this potentially actionable entity.ObjectivesThis case study aims to report a milder phenotype of a patient with NAXE gene mutation and his longitudinal follow-up of more than 20 years.Case reportA 24-year-old man first became symptomatic in infancy with frequent initial neurological decompensations in the setting of infections with subsequent clinical improvement followed by stability with residual cerebellar dysfunction. Clinical features noted over the years include chronic ataxia, nystagmus, ptosis, mild spasticity of lower limbs, and neuropsychiatric symptoms. Cerebellar and spinal cord atrophy were noted in cranial and spinal MR imaging. Biallelic homozygous variants in the NAXE gene (c.733 A>C) were identified on whole exome sequencing. Symptom management included the initiation of a mitochondrial cocktail with carnitine, coenzyme Q, and thiamine. Subsequently, niacin (Vitamin B3), which is involved in the cellular biosynthesis of NAD+, was added, given its potentially beneficial therapeutic impact.ConclusionA missense homozygous variant in the NAXE gene is described in this patient with a milder clinical phenotype of the disease. Supplementation with niacin in addition to a mitochondrial cocktail presents a potential supportive therapeutic option to reduce disease progression.

Abstract Glucocorticoid excess adversely affects male reproduction. This study evaluates effects of pharmacological doses of niacin on testicular structure and function in dexamethasone‐treated rats. Adult rats (48) were randomly assigned to 6 equal groups: (1) Negative control (NC): normal rats; (2) Positive control (PC): dexamethasone at 7 mg/kg/day by intraperitoneal injections for 7 days; groups 3–6 (N50, N100, N200, and N400): dexamethasone and concomitant treatment with niacin at 50, 100, 200, and 400 mg/kg/day by oral gavages. Testicular weight and volume of PC rats were significantly lower than the NC group (p

BackgroundDespite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of nicotinamide adenine dinucleotide (NAD+) precursor. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on weight loss, adiponectin, and leptin.MethodsScopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss and related hormones effects of NAD+ precursor. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.ResultsTwenty two treatment arms with 5,144 participants’ were included in this systematic review and meta-regression analysis. The pooled findings showed that NAD+ precursor supplementation has an effect on lowering BMI (weighted mean difference (WMD): −0.19 kg/m2, 95% confidence interval (CI): −0.29 to −0.09, p

Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions. GPR109A, a Gi protein-coupled receptor, has emerged as an important therapeutic target for controlling inflammation in various tissues and organs. In this review, we summarized current data about the role of GPR109A in neuroinflammation. Specifically, we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, and pathological pain conditions.

Abstract 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.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

A 60-day feeding trial was conducted to determine the effects of the interaction of dietary niacin and lipid on the growth, antioxidant capacity and lipid metabolism in male Eriocheir sinensis. A total 162 crabs (initial weight, 33.27 ± 0.84 g) were fed with six semi-purified diets containing L6N0 (6% lipid and 0 mg/kg niacin), L6N400 (6% lipid and 400 mg/kg niacin), L6N800 (6% lipid and 800 mg/kg niacin), L12N0 (12% lipid and 0 mg/kg niacin), L12N400 (12% lipid and 400 mg/kg niacin), L12N800 (12% lipid and 800 mg/kg niacin), respectively. Elevated levels of niacin and lipid improved growth performance of crabs, but there were no significant differences. Crabs fed with 400 mg/kg niacin diets had higher hepatopancreas index (HSI) and lipase (LPS) than that of the other groups. Niacin promoted the accumulation of lipid in the hepatopancreas, but excessive accumulation led to more oxidative stress in crabs. In conclusion, excess lipid and niacin enhanced the growth performance of male Chinese mitten crabs by promoting the accumulation of lipid in the body at the expense of impairing their immune capacity. Crabs fed with 6% lipid and 400 mg/kg niacin diet had an advantage in lipid metabolism, without a significant decrease in antioxidant capacity, achieving a balance in growth performance and immunity.

Legumes have been recognised as healthy and environmentally friendly protein sources. Knowledge about the vitamin B contents in legume ingredients and extrudates is scarce. In this study, we investigated thiamin, riboflavin, niacin, and folate in various faba bean, lupin, and pea ingredients. Further, the retention of B vitamins in high moisture extrusion was studied. Prior to liquid chromatographic determinations of thiamin, riboflavin, niacin, and folate, vitamins were extracted by acid hydrolysis (niacin), enzymatic treatment (folate), or their combination (thiamin and riboflavin). The contents (on a dry matter basis) varied greatly among different ingredients: the thiamin content was 0.2–14.2 µg/g; riboflavin, 0.3–5.9 µg/g; niacin, 8.8–35.5 µg/g, and folate, 45–1453 ng/g. Generally, the highest levels were in flours and protein concentrates, whereas low levels were observed in isolates. The retention of B vitamins was excellent in high moisture extrusion, except for folate in faba bean, where the folate contents were 42–67% lower in the extrudates than in the respective ingredient mixtures. In terms of both vitamin B contents and their retention, extrudates containing substantial amounts of flour or protein concentrate are promising plant-based sources of thiamin, riboflavin, niacin, and folate.

The present study investigates the theoretical basis for maintaining normal physiological functions in heat-stressed beef cattle by exploring the effects of niacin supplementation on the permeability of the rumen epithelial cell barrier. Herein, 12 Jinjiang bulls with an average weight of approximately 400 ± 20.0 kg were randomly divided into three groups, thermoneutral (TN), heat-stressed (HS), and heat-stressed niacin-supplemented (HN) groups, with 4 bulls in each group. The experiment spanned 70 days, and the plasma concentrations of D-lactic acid, diamine oxidase (DAO), lipopolysaccharides (LPSs), and inflammatory cytokines were analyzed. Additionally, we assessed the gene expression of tight junction proteins to understand the effect of niacin supplementation on heat-stressed beef cattle. Our results revealed that heat stress significantly increased the D-lactic acid and LPS levels in beef cattle plasma on days 30 and 45 of the experiment (p < 0.05). Moreover, it led to a significant rise in DAO levels on day 30 (p < 0.05). Niacin supplementation significantly reduced the LPS levels on day 30 (p < 0.05). Heat stress significantly elevated the plasma concentrations of inflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) (p < 0.05), while reducing the IL-4 concentration (p < 0.05). However, niacin supplementation effectively mitigated the concentrations of these inflammatory factors by reducing IL-1β, IL-2, IL-6, and TNF-α concentrations and increasing IL-4 concentrations. The mRNA expressions of tight junction proteins zonula occluden-1 (ZO-1), claudin-1, claudin-4, and claudin-7 were significantly downregulated (p < 0.05) in the HS group compared to those in the TN group, and those of ZO-1 and occludin were significantly upregulated (p < 0.05) in the HN group compared to those in the HS group. Notably, no significant differences were observed in ruminal papillae length and width among the studied groups (p > 0.05). Our findings indicate that heat stress adversely impacted the tight junction structure of the rumen epithelium, leading to a significant reduction in the expression of tight junction protein mRNA. Consequently, heat stress impaired the rumen mucosal barrier function, resulting in increased intestinal permeability. The mechanism underlying this effect may be associated with the decreased expression of tight junction protein genes in the rumen epithelial cells. However, niacin supplementation mitigated the detrimental effects of heat stress on intestinal permeability in beef cattle and increased the expression of tight junction protein genes in the rumen epithelium, thereby effectively protecting the rumen barrier in heat-stressed beef cattle. These results highlight the potential of nicotinic acid as a protective agent against the negative impacts of heat stress on intestinal integrity in beef cattle.

The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by Staphylococcus aureus and Listeria monocytogenes. (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body’s natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.

Abstract Background Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNA Lys gene at position m.8344A > G. Defective tRNALys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently limited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements. Methods We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carrying different loads of the m.8344A > G mutation. The first strategy was aimed at inducing mitochondrial biogenesis directly, over-expressing the master regulator PGC-1α, or indirectly, through the treatment with nicotinic acid, a NAD+ precursor. The second was aimed at stimulating the removal of damaged mitochondria through prolonged rapamycin treatment. Results The first approach slightly increased mitochondrial protein expression and respiration in the wild type and intermediate-mutation load cells, but was ineffective in high-mutation load cell lines. This suggests that induction of mitochondrial biogenesis may not be sufficient to rescue mitochondrial dysfunction in MERRF cells with high-mutation load. The second approach, when administered chronically (4 weeks), induced a slight increase of mitochondrial respiration in fibroblasts with high-mutation load, and a significant improvement in fibroblasts with intermediate-mutation load, rescuing completely the bioenergetics defect. This effect was mediated by increased mitochondrial biogenesis, possibly related to the rapamycin-induced inhibition of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and the consequent activation of the Transcription Factor EB (TFEB). Conclusions Overall, our results point to rapamycin-based therapy as a promising therapeutic option for MERRF.

Objective: To establish a method for the determination of nine vitamin B components in vitamin B tablets by high performance liquid chromatography-diode array detector (HPLC-DAD). Method: Folic acid was ultrasonically extracted with 0.3% ammonia solution, biotin, vitamin B12 and pantothenate acid were ultrasonically extracted with water, the vitamins B1, B2, B6, niacin and nicotinamide were ultrasonically extracted by 0.1% hydrochloric acid, separated by C18 column with methanol-0.1 mol/L potassium dihydrogen phosphate solution as the mobile phase for gradient elution. Pantothenate acid and biotin were detected at the wavelength of 205 nm, vitamins B1, B2, niacin and nicotinamide were detected at the wavelength of 256 nm, vitamins B6 and folic acid were detected at the wavelength of 287 nm, vitamins B12 was detected at the wavelength of 361 nm. Results: The results showed that the nine components could be separated well, and the linear relationship was good in their linear range. The average recoveries were 91.8%~106.9%, RSD were 0.2%~4.8%, and the detection limit of the method were 0.05~4.7 mg/kg. Conclusion: This method is rapid, simple, accurate and repeatable. It can quickly complete the determination of nine vitamin B components in health food vitamin B tablets and reduce the cost.

Introduction: B vitamins are necessary for the proper functioning of the nervous system, taking part in the synthesis of neurotransmitters, RNA and DNA and acting as cofactors in many cellular metabolic pathways. The body does not store them, so they need to be replaced daily. Mild deficiencies can cause non-specific neuropsychiatric disorders, and deep and persistent - serious, fatal disease states that require intensive supplementation, such as beriberi disease or Korsakoff's syndrome. Materials and methods: My work is based on the articles published in PubMed, medical books and websites. I was looking for the key words such as ‘biotin‘, ‘brain’, ‘homocysteine’, ‘niacin’, ‘pantothenic acid’, ‘riboflavin’, ‘thiamin’, ‘neuropathy’. Results: B vitamins seem to enhance the analgesic effect of NSAIDs. There is evidence of supportive action in the treatment of low back pain and diabetic neuropathy. There is no reliable evidence of improved cognitive function in patients with Alzheimer's disease or other types of dementia. Conclusions: due to the low toxicity, very few side effects and experimental findings, it seems reasonable to administer B vitamins in numerous pain syndromes, such as neuropathies and back pain syndromes. However, we need more randomized clinical trials to create universal recommendations and finally confirm the positive effects of these substances in neurological diseases.

BackgroundThe PNPLA3 p.I148M impact on fat accumulation can be modulated by nutrients. Niacin (Vitamin B3) reduced triglycerides synthesis in in vitro and in vivo NAFLD models.ObjectivesIn this study, we aimed to investigate the niacin-I148M polymorphism crosstalk in NAFLD patients and examine niacin’s beneficial effect in reducing fat by exploiting hepatoma cells with different PNPLA3 genotype.DesignWe enrolled 172 (Discovery cohort) and 358 (Validation cohort) patients with non-invasive and histological diagnosis of NAFLD, respectively. Dietary niacin was collected from food diary, while its serum levels were quantified by ELISA. Hepatic expression of genes related to NAD metabolism was evaluated by RNAseq in bariatric NAFLD patients (n = 183; Transcriptomic cohort). Hep3B (148I/I) and HepG2 (148M/M) cells were silenced (siHep3B) or overexpressed (HepG2I148+) for PNPLA3, respectively.ResultsIn the Discovery cohort, dietary niacin was significantly reduced in patients with steatosis ≥ 2 and in I148M carriers. Serum niacin was lower in subjects carrying the G at risk allele and negatively correlated with obesity. The latter result was confirmed in the Validation cohort. At multivariate analysis, the I148M polymorphism was independently associated with serum niacin, supporting that it may be directly involved in the modulation of its availability. siHep3B cells showed an impaired NAD biosynthesis comparable to HepG2 cells which led to lower niacin efficacy in clearing fat, supporting a required functional protein to guarantee its effectiveness. Conversely, the restoration of PNPLA3 Wt protein in HepG2I148+ cells recovered the NAD pathway and improved niacin efficacy. Finally, niacin inhibited de novo lipogenesis through the ERK1/2/AMPK/SIRT1 pathway, with the consequent SREBP1-driven PNPLA3 reduction only in Hep3B and HepG2I148M+ cells.ConclusionsWe demonstrated a niacin-PNPLA3 I148M interaction in NAFLD patients which possibly pave the way to vitamin B3 supplementation in those with a predisposing genetic background.

Abstract Background Hyperphosphatemia is a common complication of end-stage renal disease (ESRD) and particularly affects hemodialysis (HD) patients. Elevated serum phosphorus contributes to the development of secondary hyperparathyroidism, chronic kidney disease–mineral bone disorder (CKD-MBD), metastatic calcifications and calcific uremic arteriolopathy. There is a significant association between hyperphosphatemia and increased morbidity and mortality in ESRD patients including cardiovascular morbidity and mortality, and it is also associated with prolonged hospitalization of HD patients. This study aim to evaluate the serum phosphorus lowering effect of niacin in HD patients. Results There was a decrease in phosphate values during the first 3 months of the study in the niacin group, with a significant change in phosphate level at the third month (5.90 ± 0.52 vs. 6.42 ± 0.65 (mEq/l); P

Currently pellagra is usually the subject of dermatological or non-dermatological case reports. Since the first description of the disease, its cause has remained unknown for many years. There were no known methods of prevention and treatment. For two centuries, pellagra was an incurable disease and caused several hundred thousand deaths in Europe and North America. Research by clinicians and scientists has made it possible to refute the common theory of the infectious etiology of the disease and link the disease epidemic to maize, which was then the primary source of food for the poor. Consumption limited to this grain resulted in an extreme deficiency of niacin (vitamin B3) and symptoms of pellagra. Niacin supplementation caused the lesions to regress, and became crucial to combat the epidemic. The article presents the first descriptions, the greatest outbreaks of the epidemic and the stormy process of discovering data on the etiology of pellagra, as well as typical clinical features of the diseases.

Introduction: Electrolyte abnormalities are one of the most common problems in hemodialysis patients. Objectives: The present study was conducted to investigate the effect of niacin on the levels of sodium, phosphorus, calcium, intact parathormone (iPTH), alkaline phosphatase (ALP) and vitamin D in hemodialysis patients. Patients and Methods: In the present double-blinded randomized clinical trial, hemodialysis patients with phosphorus of more than 4.5 mg/dL were included in the study and were treated with niacin. The dose of niacin was increased from 50 mg to 100 mg/d in two stages on a monthly basis. Tests related to the levels of phosphorus, sodium, vitamin D, and calcium were determined before and after the intervention, and the side effects of the treatment were recorded accordingly. Data were analyzed through SPSS version 16. Results: After the intervention, the serum levels of calcium, vitamin D, and sodium increased significantly (P0.05). There was no significant difference in the serum levels of calcium, phosphate, vitamin D, sodium, iPTH, and ALP during the intervention in the both men and women (P>0.05). Side effects were not reported in any of the patients. Conclusion: Niacin can increase vitamin D, sodium and calcium and decreased serum levels of phosphate and iPTH in hemodialysis patients. Therefore, it can be administered as an effective and safe supplement in the hemodialysis patients. Trial Registration: This trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20190702044076N2; https://en.irct.ir/trial/66567, ethical code #IR.SKUMS. REC.1400.079).

The widely used lipid-lowering drug niacin was reported to increase blood glucose in diabetes. How does niacin regulate β Cell function in diabetic patients remains unclear. This study aimed to investigate the effect of niacin on β cell lipotoxicity in vitro and in vivo. Niacin treatment sensitized the palmitate-induced cytotoxicity and apoptosis in INS-1 cells. In addition, palmitate significantly increased the niacin receptor GPR109A and PPARγ2 levels, which could be further boosted by niacin co-treatment, creating a vicious cycle. In contrast, knocking down of GPR109A could reverse both PPARγ2 expression and niacin toxicity in the INS-1 cells. Interestingly, we found that GLP-1 receptor agonist exendin-4 showed similar inhibitive effects on the GPR109A/PPARγ2 axis and was able to reverse niacin induced lipotoxicity in INS-1 cells. In diet-induced obesity (DIO) mouse model, niacin treatment resulted in elevated blood glucose, impaired glucose tolerance and insulin secretion, accompanied by the change of islets morphology and the decrease of β cell mass. The combination of niacin and DPP-4 inhibitor sitagliptin can improve glucose tolerance, insulin secretion and islet morphology and β cell mass, even better than sitagliptin alone. Our results show that niacin increased β cell lipotoxicity partially through upregulation of GPR109A and PPARγ2, which can be alleviated by incretin drugs. We provide a new mechanism of niacin toxicity, and suggest that the combination of niacin and incretin may have better blood glucose and lipid control effect in clinical practice.

Abstract The modified electrode–analyte interaction is critical in establishing the sensing mechanism and in developing an electrochemical sensor. Here, the niacin-modified carbon paste electrode (NC/CPE) was fabricated for electrochemical sensing applications. The two stable structures of the niacin were optimized and confirmed by the absence of negative vibrational frequency, at B3LYP and B3LYP-GD3BJ level and 6–311 g** basis set. The physical and quantum chemical quantities were used to explain the molecular stability and electronic structure-related properties of the niacin. The natural bond orbital (NBO) analysis was performed to disclose the donor–acceptor interactions that were a critical role in explaining the modifier–analyte interaction. The fabricated NC/CPE was used for the determination of folic acid (FA) in physiological pH by cyclic voltammetry (CV) method. The limit of detection (LOD) for FA at NC/CPE was calculated to be 0.09 µM in the linear concentration range of 5.0 µM to 45.0 µM (0.2 M PBS, pH 7.4) by CV technique. The analytical applicability of the NC/CPE was evaluated in real samples, such as fruit juice and pharmaceutical sample, and the obtained results were acceptable. The HOMO and LUMO densities are used to identify the nucleophilic and electrophilic regions of niacin. The use of density functional theory-based quantum chemical simulations to understand the sensory performance of the modifier has laid a new foundation for fabricating electrochemical sensing platforms.

Maize (Zea mays) is the most produced crop worldwide and the second most important bio-energy plant. Huge maize monoculture is considered a threat to biodiversity in agricultural landscapes and may also contribute to the decline of European brown hares (Lepus europaeus, Pallas 1778). Indeed, the intensification of agriculture has been identified as one of the main factors responsible for the decline of brown hare populations. A reason why large maize cultures can be particularly detrimental to animals consuming this plant is its poor nutritional value with respect to niacin. In this study, we investigated the effects of the proportion of area under maize crops on liver concentrations of niacin in free-living hares, on the reproductive output of does (females), and on the development of local populations, at nine study sites in Lower Austria. Hare numbers were estimated from spotlight counts in spring and autumn. Liver samples and uteri were obtained from hares shot in the same areas during regular autumn hunts. Number of offspring born to an individual female during the preceding reproductive period was determined by counting placental scars. Our results show a significant negative effect of the area under maize crops on liver concentrations of niacin of does and on their reproductive output. Further, we found a significant negative effect of the area under maize on the development of a population. Altogether, our findings indicate that high proportions of the area under maize crops contribute to the decline of brown hares by reduced fecundity of does and impaired development of local populations.

As one of the local pig breeds in China with a high fat rate, improving the lean meat rate of Ningxiang pigs through nutritional intervention is an urgent issue to be solved. As an important feed additive, niacin plays an important role in lipid metabolism. The purpose of this study was to investigate the regulation and mechanism of niacin on fat deposition in Ningxiang pigs. Thirty-four Ningxiang pigs (53.34 ± 2.78 kg) were randomly divided into two groups with five replicates each, with three to four Ningxiang pigs per replicate. The control group was fed a basal diet (contained 22 mg/kg niacin), and the experimental group was fed the same diet supplemented with an additional 100 mg/kg of niacin. The experimental period lasted 60 days. One Ningxiang pig was selected for slaughter sampling for each replicate. This study found that lean meat percentage of Ningxiang pigs in the experimental group was significantly increased (P < 0.05), accompanied by a significant decrease in fat percentage (P < 0.05). 16S rRNA sequencing analysis found an abundance of Streptococcus in the experimental group (P < 0.05), along with significantly decreased levels of Lactobacillus (P < 0.05). The changes in some OTUs belonging to Firmicutes, Bacteroidota, and Actinobacteriota were closely related to the changes in the fat rate and lean meat rate of Ningxiang pigs (P < 0.05). LC–MS metabolomics analysis found that about 43.75% of the differential metabolites were related to lipids and lipid-like molecules in the liver (P < 0.05). Spearman's correlation analysis showed correlations between the carcass traits, microbiota, and liver metabolites. In conclusion, niacin improves lean meat percentage and reduces fat deposition by regulating lipid metabolism and gut microbiota composition in Ningxiang pigs.

The objective of this study was to investigate the alleviation effects of niacin supplementation on beef cattle subjected to heat stress and to provide a theoretical basis for exploring the alleviation methods of heat stress environmental factors on the rumen of beef cattle. In the experiment, 36 Jinjiang bull cattle with a body weight of about 400 ± 20.0 kg were randomly divided into three treatments, each treatment contains four replicates, with three cattle in each replicate. Treatments included thermoneutral treatment (TN; temperature: 24–25°C, humidity: 45–55%), heat stress treatment, exposure to environmental temperature (HS; average THI: 82.74), and heat stress supplemented with niacin treatment (HN; high temperature + 800 mg/kg NA). Measured indicators were body temperature, respiratory rate, production performances, rumen fermentations, and microbial diversity. Results showed that adding niacin reduced the body temperature and respiratory rate (P < 0.05) but had no significant effect on the production performances compared with heat-stressed beef cattle. HS treatment significantly increased body temperature and respiratory rate (P < 0.01), while decreasing the content of acetic acid, butyric acid, and total volatile fatty acids (P < 0.05) compared with the TN treatment. Supplement of niacin did not affect ruminal fermentation parameters (P > 0.05) but had a decreased tendency on A/P (P < 0.1). Microbial diversity results showed that, at the phylum level, the relative abundance of Desulfobacterota in the HS treatment was increased compared with TN and HN treatment (P < 0.05). At the genus level, the relative abundance of Succiniclasticum and Family_XIII_AD3011 group in the HN treatment significantly proliferated compared with the HS treatment (P < 0.05). In conclusion, niacin supplementation may alleviate heat stress by proliferating those bacteria belonging to the phylum Succiniclasticum, which may further contribute to the digestion of cellulose and the improvement of the metabolic function of Jinjiang cattle under heat-stress conditions.

Wallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD+ synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD+ degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability of these events to therapeutic interventions remain unclear. Here we explored pharmacological strategies that modulate NMN and NAD+ metabolism, namely the inhibition of the NMN-synthesizing enzyme NAMPT, activation of the nicotinic acid riboside (NaR) salvage pathway and inhibition of the NMNAT2-degrading DLK MAPK pathway in an axotomy model in vitro. Results show that NAMPT and DLK inhibition cause a significant but time-dependent delay of WD. These time-dependent effects are related to NMNAT2 degradation and changes in NMN and NAD+ levels. Supplementation of NAMPT inhibition with NaR has an enhanced effect that does not depend on timing of intervention and leads to robust protection up to 4 days. Additional DLK inhibition extends this even further to 6 days. Metabolite analyses reveal complex effects indicating that NAMPT and MAPK inhibition act by reducing NMN levels, ameliorating NAD+ loss and suppressing SARM1 activity. Finally, the axonal NAD+/NMN ratio is highly predictive of cADPR levels, extending previous cell-free evidence on the allosteric regulation of SARM1. Our findings establish a window of axon protection extending several hours following injury. Moreover, we show prolonged protection by mixed treatments combining MAPK and NAMPT inhibition that proceed via complex effects on NAD+ metabolism and inhibition of SARM1.

The current study investigated the neuroprotective activity of some drugs and nutriceuticals with antioxidant and anti-inflammatory potential on the pathogenesis of Parkinson’s disease (PD). Rats were categorized into seven groups: Rats received tween80 daily for 5 weeks as a control group, MnCl2 (10 mg/kg, i.p) either alone (group II) or in combination with vinpocetine (VIN) (20 mg/kg) (group III), punicalagin (PUN) (30 mg/kg) (group IV), niacin (85 mg/kg) (group V), vitamin E (Vit E) (100 mg/kg) (group VI) or their combination (group VII). Motor activities was examined using open-field and catalepsy. Striatal monamines, acetylcholinesterase, excitatory/inhibitory neurotransmitters, redox status, pro-oxidant content, brain inflammatory, apoptotic and antioxidant biomarkers levels were assessed. Besides, histopathological investigations of different brain regions were determined. Groups (IV –GVII) showed improved motor functions of PD rats. Applied drugs significantly increased the brain levels of monoamines with the strongest effect to PUN. Meanwhile, they significantly decreased levels of acetylcholinesterase with a strongest effect to PUN. Moreover, they exhibited significant neuronal protection and anti-inflammatory abilities through significant reduction of the brain levels of COX2, TNF-α and Il-1β with a strongest effect to the PUN. Interestingly; groups (IV – GVII) showed restored glutamate/GABA balance and exhibited a pronounced decrease in caspase-3 content and GSK-3β protein expression levels. In addition, they significantly increased Bcl2 mRNA expression levels with a strongest effect for PUN. All these findings were further confirmed by the histopathological examinations. As a conclusion, we propose VIN and PUN to mitigate the progression of PD via their antioxidant, anti-inflammatory, anti-apoptotic, neurotrophic and neurogenic activities.

Abstract Background Dyslipidaemia is a group of abnormalities that predispose people to heart disease. The index of nutritional quality (INQ) is a tool for qualitative and quantitative nutritional assessment, which has special significance in assessing clinical nutritional problems. The objective of this study was to determine the association between the INQ and lipid profile in adult women. Methods This was a cross‐sectional study on 360 healthy women referring to the nutrition clinic of Shohadaye Tajrish hospital, Tehran, Iran. Calorie and nutrient intake were assessed using a validated food frequency questionnaire. The amount of physical activity was estimated using a validated International Physical Activity Questionnaire. To measure serum lipid levels, 5 ml of venous blood samples was taken from the participants. Results The results showed a negative association between total cholesterol and the INQ of niacin (B = −0.110, p = .02) and between high‐density lipoprotein cholesterol with the INQ of biotin (B = −0.119, p = .01). Also, a positive association was found between triglyceride and the INQ of B6 (B = 0.096, p = .04). The results remained significant after adjusting for body mass index, waist circumference and total energy intake (except for niacin). Conclusions Findings of the present study suggest that a diet rich in niacin and low in vitamin B6 and biotin may be associated with an improved lipid profile that reduces lipid‐related diseases such as fatty liver, metabolic syndrome and cardiovascular disease. Further studies are needed to confirm these findings and to identify the underlying mechanisms.

Dietary vitamin B3 components, such as nicotinamide and nicotinic acid, are precursors to the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD+). NAD+ levels are thought to decline with age and disease. While the drivers of this decline remain under intense investigation, strategies have emerged seeking to functionally maintain NAD+ levels through supplementation with NAD+ biosynthetic intermediates. These include marketed products, such as nicotinamide riboside (NR) and its phosphorylated form (NMN). More recent developments have shown that NRH (the reduced form of NR) and its phosphorylated form NMNH also increases NAD+ levels upon administration, although they initially generate NADH (the reduced form of NAD+). Other means to increase the combined levels of NAD+ and NADH, NAD(H), include the inhibition of NAD+-consuming enzymes or activation of biosynthetic pathways. Multiple studies have shown that supplementation with an NAD(H) precursor changes the profile of NAD(H) catabolism. Yet, the pharmacological significance of NAD(H) catabolites is rarely considered although the distribution and abundance of these catabolites differ depending on the NAD(H) precursor used, the species in which the study is conducted, and the tissues used for the quantification. Significantly, some of these metabolites have emerged as biomarkers in physiological disorders and might not be innocuous. Herein, we review the known and emerging catabolites of the NAD(H) metabolome and highlight their biochemical and physiological function as well as key chemical and biochemical reactions leading to their formation. Furthermore, we emphasize the need for analytical methods that inform on the full NAD(H) metabolome since the relative abundance of NAD(H) catabolites informs how NAD(H) precursors are used, recycled, and eliminated.

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.

In vitro maturation (IVM) is an important reproductive technology used to produce embryos in vitro. However, the developmental potential of oocytes sourced for IVM is markedly lower than those matured in vivo. Previously, NAD+-elevating treatments have improved oocyte quality and embryo development in cattle and mice, suggesting that NAD+ is important during oocyte maturation. The aim of this study was to examine the effects of nicotinic acid (NA), nicotinamide (NAM) and nicotinamide mononucleotide (NMN) on oocyte maturation and subsequent embryo development. Porcine oocytes from small antral follicles were matured for 44 h in a defined maturation medium supplemented with NA, NAM and resveratrol or NMN. Mature oocytes were artificially activated and presumptive zygotes cultured for 7 days. Additionally, oocytes were matured without treatment then cultured for 7 days with NMN. Supplementing the IVM medium with NA improved maturation and blastocyst formation while NAM supplementation improved cleavage rates compared with untreated controls. Supplementing the IVM or embryo culture media with NMN had no effect on maturation or embryo development. The results show that supplementing the maturation medium with NA and NAM improved maturation and developmental potential of porcine oocytes.

Abstract KPT-9274 is a phase 1 first-in-class dual PAK4/NAMPT inhibitor for solid tumor and non-Hodgkin’s lymphoma. It demonstrates pre-clinical efficacy toward a broad spectrum of acute myeloid leukemia (AML) subtypes by inhibiting NAMPT-dependent NAD+ production. NAMPT is the rate-limiting enzyme in the salvage metabolic pathway leading to NAD+ generation. Tumor cells which are deficient in de novo pathway enzyme NAPRT1 are addicted to NAMPT. In clinical trials, treatment with NAMPT inhibitors resulted in dose-limiting toxicities. In order to dissect the mechanism of toxicity, mice were treated with KPT-9274 and resulting toxicities were characterized histopathologically and biochemically. KPT-9274 treatment caused gender-dependent stomach and kidney injuries and anemia. Female mice treated with KPT-9274 had EPO deficiency and associated impaired erythropoiesis. KPT-9274 treatment suppressed SIRT3 expression and concomitantly upregulated acetyl-manganese superoxide dismutase (MnSOD) in IMCD3 cells, providing a mechanistic basis for observed kidney toxicity. Importantly, niacin supplementation mitigated KPT-9274-caused kidney injury and EPO deficiency without affecting its efficacy. Altogether, our study delineated the mechanism of KPT-9274-mediated toxicity and sheds light onto developing strategies to improve the tolerability of this important anti-AML inhibitor.