Characteristics of Nutrition and Metabolism in Dogs and Cats.

Domestic dogs and cats have evolved differentially in some aspects of nutrition, metabolism, chemical sensing, and feeding behavior. The dogs have adapted to omnivorous diets containing taurine-abundant meat and starch-rich plant ingredients. By contrast, domestic cats must consume animal-sourced foods for survival, growth, and development. Both dogs and cats synthesize vitamin C and many amino acids (AAs, such as alanine, asparagine, aspartate, glutamate, glutamine, glycine, proline, and serine), but have a limited ability to form de novo arginine and vitamin D3. Compared with dogs, cats have greater endogenous nitrogen losses and higher dietary requirements for AAs (particularly arginine, taurine, and tyrosine), B-complex vitamins (niacin, thiamin, folate, and biotin), and choline; exhibit greater rates of gluconeogenesis; are less sensitive to AA imbalances and antagonism; are more capable of concentrating urine through renal reabsorption of water; and cannot tolerate high levels of dietary starch due to limited pancreatic α-amylase activity. In addition, dogs can form sufficient taurine from cysteine (for most breeds); arachidonic acid from linoleic acid; eicosapentaenoic acid and docosahexaenoic acid from α-linolenic acid; all-trans-retinol from ß-carotene; and niacin from tryptophan. These synthetic pathways, however, are either absent or limited in all cats due to (a) no or low activities of key enzymes (including pyrroline-5-carboxylate synthase, cysteine dioxygenase, ∆6-desaturase, ß-carotene dioxygenase, and quinolinate phosphoribosyltransferase) and (b) diversion of intermediates to other metabolic pathways. Dogs can thrive on one large meal daily, select high-fat over low-fat diets, and consume sweet substances. By contrast, cats eat more frequently during light and dark periods, select high-protein over low-protein diets, refuse dry food, enjoy a consistent diet, and cannot taste sweetness. This knowledge guides the feeding and care of dogs and cats, as well as the manufacturing of their foods. As abundant sources of essential nutrients, animal-derived foodstuffs play important roles in optimizing the growth, development, and health of the companion animals.

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.

Contribution of Beef to Key Nutrient Intakes and Nutrient Adequacy in Pregnant and Lactating Women: NHANES 2011-2018 Analysis.

Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B-vitamins. The objective was to assess the association of beef intake with nutrient intake and adequacy among pregnant and lactating women using 24-h dietary recall data. Usual intakes from foods were determined with the National Cancer Institute (NCI) method and % population below Estimated Average Requirement (EAR) or above Adequate Intake (AI) were estimated. A high proportion of pregnant and lactating women had inadequate intakes for vitamin D (94%), vitamin E (82%), vitamin C (52%), and vitamin A (50%), magnesium (35%), folate (31%), zinc (25%), and vitamin B6 (22%); only 4% and 35% met AI for choline and potassium, respectively. About 67% of pregnant and lactating women were beef consumers, consuming 49 g beef/day. Beef consumers had higher intakes (p < 0.05) of energy, protein, calcium, iron, phosphorus, selenium, sodium, zinc, thiamin, riboflavin, and niacin, and a higher proportion (p < 0.05) met nutrient recommendations for protein, calcium, iron, zinc, thiamin, riboflavin, niacin, vitamin B6, and vitamin B12 compared to non-consumers. In conclusion, pregnant and lactating women generally have inadequate nutrient intakes from their diets. Beef consumers have higher intakes and adequacy for certain nutrients, many of which are inherently available in beef or in foods eaten with beef.

[Distribution of usual vitamin intake and prevalence of inadequate intake among Chinese adults in 2015].

OBJECTIVE: To estimate the usual vitamin intake and the prevalence of inadequate intakes among Chinese adults in 2015, and to provide a scientific basis for developing nutrition intervention strategies and measures for target populations. METHODS: Data was drawn from the Chinese Nutrition and Health Surveillance 2015-2017, a nationally representative cross-sectional study. The multistage stratified whole-group random sampling method was used to draw participants from 298 surveillance sites in 31 provinces(autonomous regions and municipalities). Participants with no available information or abnormal energy intake were excluded, and finally, a total of 72 231 participants aged 18 years and older were included in the current study. The dietary data of the participants were collected by the 24-hour dietary recall method combined with the condiment weighing method for three consecutive days. The National Cancer Institute method was used to estimate the distribution of the usual intake of vitamin B_1(thiamine), vitamin B_2(riboflavin), niacin, vitamin C(ascorbic acid), and vitamin E(tocopherol), and the prevalence of inadequate intake was evaluated based on estimated average requirement or adequate intake from the Chinese Dietary Reference Intakes 2023. RESULTS: The usual intake of vitamin E, vitamin C, vitamin B_1, vitamin B_2 and niacin were 27.93 mg/d, 77.67 mg/d, 0.78 mg/d, 0.62 mg/d and 13.15 mg/d, respectively. The prevalence of inadequate intake was, in descending order, vitamin B_2(95.98%), vitamin B_1(86.73%), vitamin C(63.70%), niacin(39.81%), and vitamin E(21.17%). The prevalence of inadequate vitamin E, vitamin C, vitamin B_1 and niacin intake among females was higher than among males(P<0.01). Overall, the prevalence of inadequate vitamin intake increased with age. Rural residents had a higher prevalence of inadequate intake of vitamin C, vitamin B_2 and niacin than urban residents(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing education levels. The prevalence of inadequate intake of these five vitamins was higher among participants with lower income levels than those with middle or high income(P<0.01). Participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity and had a higher prevalence of inadequate intake of vitamin C than those with obesity. However, participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity, with the differences being statistically significant(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing physical activity intensity. CONCLUSION: In 2015, the usual intake of dietary vitamins of Chinese adults was low. There are differences in usual intakes of vitamins and prevalence of inadequate vitamin intake for adults aged 18 years and above in males and females, different age groups, urban and rural areas, education levels, household income levels, body mass index and physical activity intensity.

Opposing Effects of Nutritional Supply on Bone Health at Different Ages: Based on the National Health and Nutrition Examination Survey Database.

(1) Background: Nutrients play an essential role in bone health, whether in achieving peak bone mineral density (BMD) or maintaining bone health. This study explores the relationship between nutrient supply and femoral bone health at different ages. (2) Methods: A total of 5603 participants meeting the inclusion and exclusion criteria were included in this study using the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2010, 2013 to 2014, and 2017 to 2018. Femoral bone mineral density and bone status were dependent variables, and dietary nutrient intake and nutrient intake status were independent variables. The relationship between dietary nutrient intake and bone mineral density was explored, and the importance of nutrients affecting bone status was analyzed through a neural network model. At the same time, we investigated the relationship between nutrient intake and bone status. (3) Results: The peak of age and femoral bone mineral density appeared at 20 years old in our study. After grouping by age, logistic regression analysis showed that before 20 years old, without adjusting other variables, high-fat diet was more likely to have normal bone mass than appropriate fat diet (OR: 4.173, 95%CI: 1.007-17.289). After adjusting for all demographic factors, niacin intake (OR: 1.062, 95%CI: 1.019-1.108) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.627, 95%CI: 0.408-0.965) was not. After 20 years old, after adjusting for carbohydrate, protein, vitamin B6, niacin, dietary fat, vitamin B2, and vitamin B12, vitamin B2 intake (OR: 1.153, 95%CI: 1.04-1.278) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.842, 95%CI: 0.726-0.976) was not. After adjusting for all confounding factors, vitamin B2 intake (OR: 1.288, 95%CI: 1.102-1.506) was beneficial for normal bone mass. In addition, we found that even if there was no statistical significance, the effects of high-fat diet on bone mass were different at different ages. (4) Conclusions: By conducting an in-depth analysis of the NHANES database, this study reveals that dietary factors exert divergent effects on bone health across different age groups, implying the necessity of implementing tailored dietary strategies to maintain optimal bone health at distinct life stages.

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.

The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor.

Dietary Niacin Intake and Mortality Among Individuals With Nonalcoholic Fatty Liver Disease.

Importance: Evidence regarding the effect of dietary niacin intake on the risk of mortality among patients with nonalcoholic fatty liver disease (NAFLD) is scarce. Objective: To examine the association of dietary niacin intake with all-cause mortality and cardiovascular disease (CVD) mortality among individuals with NAFLD. Design, Setting, and Participants: This cohort study used data from the National Health and Nutrition Examination Survey (2003-2018). In total, 4315 adults aged 20 years or older with NAFLD were included, with NAFLD defined using the United States Fatty Liver Index. Exposure: Dietary niacin intake levels. Main Outcomes and Measures: Weighted Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios and 95% CIs for all-cause and CVD mortality. Data were analyzed March 1 to September 1, 2023. Results: This cohort study included data from 4315 participants in the analysis (mean [SD] age, 52.5 [16.2] years; 1670 participants ≥60 years [weighted, 30.9%]; 2351 men [weighted, 55.0%]). During a median (IQR) follow-up of 8.8 (4.6-11.8) years, 566 deaths were recorded, of which 197 were attributed to CVD. Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 (95% CI, 0.50-0.96) for all-cause mortality (P = .03 for trend) and 0.65 (95% CI, 0.35-1.20) for CVD mortality (P = .16 for trend). Conclusions and Relevance: Findings from this cohort study suggest that higher dietary niacin intake may be associated with lower risk of all-cause mortality among individuals with NAFLD. There was no evident inverse association between dietary niacin intake and the risk of CVD mortality.

Pilot Study of Heat-Stabilized Rice Bran Acceptability in Households of Rural Southwest Guatemala and Estimates of Fiber, Protein, and Micro-Nutrient Intakes among Mothers and Children.

Nutrient-dense, acceptable foods are needed in low-resource settings. Rice bran, a global staple byproduct of white rice processing, is rich in amino acids, fibers, and vitamins, when compared to other cereal brans. This pilot study examines the nutritional contribution of rice bran to the daily diets of mother-child pairs in rural southwest Guatemala. Thirty households were screened. Mothers (≥18 years) and children (6 to 24 months) completed 24 h dietary recalls at baseline and after 12 weeks (endline) for diet intake and diversity analyses. During biweekly visits for 12 weeks, households with <5 members received 14 packets containing 60 g of heat-stabilized rice bran, and those with ≥5 members received 28 packets. The macro- and micro-nutrient contributions of rice bran and whole, cooked black beans were included in dietary simulation models with average intakes established between the recalls and for comparison with dietary reference intakes (DRIs). A baseline child food frequency questionnaire was administered. The 27 mothers and 23 children with complete recalls were included in analyses. Daily maternal consumption of 10 g/d of rice bran plus 100 g/d of black beans resulted in all achieving at least 50% of the fiber, protein, magnesium, niacin, potassium, and thiamin DRIs. Daily child consumption of 3 g/d of rice bran plus 10 g/d of black beans resulted in all achieving at least 50% of the magnesium, niacin, phosphorous, and thiamine DRIs. For 15/17 food categories, male children had a higher intake frequency, notably for animal-source foods and coffee. Dietary rice bran coupled with black beans could improve nutritional adequacy, especially for fiber and key micro-nutrients, with broader implications for addressing maternal and child malnutrition in low-resource settings.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Association of dietary niacin intake with the prevalence and incidence of chronic obstructive pulmonary disease.

Evidence regarding the association between dietary niacin intake and chronic obstructive pulmonary disease (COPD) is limited. Our study investigates the relationship between dietary niacin intake and the prevalance and incidence of COPD in the adult population of the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. Data on niacin intake were extracted through dietary intake interviews. COPD diagnoses were based on lung function, medical history, and medication usage. We analyzed the association between niacin consumption and COPD using multiple logistic regression and restricted cubic spline models. The study included 7055 adult participants, divided into COPD (n = 243; 3.44%) and non-COPD (n = 6812; 96.56%) groups. Those with COPD had lower average niacin intake (21.39 ± 0.62 mg/day) compared to the non-COPD group (25.29 ± 0.23 mg/day, p < 0.001). In the adjusted multivariable model, the odds ratios (OR) and 95% confidence intervals (CI) for COPD in the highest versus lowest quartile of dietary niacin intake were 0.55 (0.33 to 0.89, P for trend = 0.009). Subgroup analysis, after adjustment for various variables, revealed no significant interaction effects. Dietary niacin intake was inversely associated with COPD prevalence in US adults. Participants with the highest dietary niacin intake demonstrated the lowest odds of COPD. The potential of dietary niacin supplementation as a strategy to mitigate COPD warrants further investigation.

Chronic Ethanol Intake Impairs Niacin Nutritional Status in Mice.

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol in the liver, ethanol consumption can be a factor to impair niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic ethanol intake on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets with or without 15% ethanol for 35 d. The mice fed 4 mg/kg nicotinic acid diet with ethanol showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the mice without ethanol. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic ethanol intake failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic ethanol-induced growth retardation, their body weight rapidly increased. These results show that chronic ethanol intake impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic ethanol intake increases niacin requirement by increase of NAD consumption.

Inhibitors of NAD+ Production in Cancer Treatment: State of the Art and Perspectives.

The addiction of tumors to elevated nicotinamide adenine dinucleotide (NAD+) levels is a hallmark of cancer metabolism. Obstructing NAD+ biosynthesis in tumors is a new and promising antineoplastic strategy. Inhibitors developed against nicotinamide phosphoribosyltransferase (NAMPT), the main enzyme in NAD+ production from nicotinamide, elicited robust anticancer activity in preclinical models but not in patients, implying that other NAD+-biosynthetic pathways are also active in tumors and provide sufficient NAD+ amounts despite NAMPT obstruction. Recent studies show that NAD+ biosynthesis through the so-called "Preiss-Handler (PH) pathway", which utilizes nicotinate as a precursor, actively operates in many tumors and accounts for tumor resistance to NAMPT inhibitors. The PH pathway consists of three sequential enzymatic steps that are catalyzed by nicotinate phosphoribosyltransferase (NAPRT), nicotinamide mononucleotide adenylyltransferases (NMNATs), and NAD+ synthetase (NADSYN1). Here, we focus on these enzymes as emerging targets in cancer drug discovery, summarizing their reported inhibitors and describing their current or potential exploitation as anticancer agents. Finally, we also focus on additional NAD+-producing enzymes acting in alternative NAD+-producing routes that could also be relevant in tumors and thus become viable targets for drug discovery.

A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk.

Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma from stable cardiac patients in a prospective discovery cohort (n = 1,162 total, n = 422 females) suggested that niacin metabolism was associated with incident major adverse cardiovascular events (MACE). Serum levels of the terminal metabolites of excess niacin, N1-methyl-2-pyridone-5-carboxamide (2PY) and N1-methyl-4-pyridone-3-carboxamide (4PY), were associated with increased 3-year MACE risk in two validation cohorts (US n = 2,331 total, n = 774 females; European n = 832 total, n = 249 females) (adjusted hazard ratio (HR) (95% confidence interval) for 2PY: 1.64 (1.10-2.42) and 2.02 (1.29-3.18), respectively; for 4PY: 1.89 (1.26-2.84) and 1.99 (1.26-3.14), respectively). Phenome-wide association analysis of the genetic variant rs10496731, which was significantly associated with both 2PY and 4PY levels, revealed an association of this variant with levels of soluble vascular adhesion molecule 1 (sVCAM-1). Further meta-analysis confirmed association of rs10496731 with sVCAM-1 (n = 106,000 total, n = 53,075 females, P = 3.6 × 10-18). Moreover, sVCAM-1 levels were significantly correlated with both 2PY and 4PY in a validation cohort (n = 974 total, n = 333 females) (2PY: rho = 0.13, P = 7.7 × 10-5; 4PY: rho = 0.18, P = 1.1 × 10-8). Lastly, treatment with physiological levels of 4PY, but not its structural isomer 2PY, induced expression of VCAM-1 and leukocyte adherence to vascular endothelium in mice. Collectively, these results indicate that the terminal breakdown products of excess niacin, 2PY and 4PY, are both associated with residual CVD risk. They also suggest an inflammation-dependent mechanism underlying the clinical association between 4PY and MACE.

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.

Cholestatic Drug-Induced Liver Injury in a Patient Taking High-Dose Niacin for Hyperlipidemia.

Niacin, an important component of a balanced diet, is central to lipid metabolism. Occasionally used to treat hyperlipidemia, niacin is widely available without a prescription, making its use often unknown to treating physicians. Severe hepatotoxicity has been reported with niacin use. In the following report, we describe a case of hospitalization for acute decompensated cirrhosis with cholestatic morphology in a patient taking self-initiated large quantities of extended-release niacin. Despite medical management and support, the patient unfortunately expired on day 16 of hospitalization. Given ease of access and unclear long-term benefit in hyperlipidemia, the current case serves to raise awareness of niacin's potential hepatotoxicity through highlighting a severe outcome. Although mode of liver injury remains unknown, the use of extended-release niacin formulations and prolonged high-dose supplementation is associated with enhanced hepatotoxicity. Careful review and counseling of commonly available supplements remains an important task of both hospital and primary care physicians.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

Novel approach for corn straw biorefineries: Production of xylooligosaccharides, lignin and ethanol by nicotinic acid hydrolysis and pentanol pretreatment.

The productive separation and conversion of corn straw offers significant prospects for the economic viability of biorefineries centered on straw resources. In this work, a graded utilization method was proposed to produce xylo-oligosaccharides (XOS), ethanol and lignin from corn straw by nicotinic acid (NA) hydrolysis and water/pentanol pretreatment. A XOS yield of 52.6 % was achieved under optimized conditions of 100 mM NA, 170 °C and 30 min. The solid residue was directly treated with water/pentanol, achieving a lignin removal rate of 79.7 %, and the total XOS yield was improved to 62.6 %. The lignin recovered from pentanol had a high purity of 97.6 %, with high phenolic OH content. Simultaneous saccharification and fermentation of final residue resulted in an ethanol yield of 92.0 %, which yielded 55.3 g/L ethanol. Thus, NA hydrolysis and water/pentanol pretreatment provided an efficient, environmentally friendly approach to fractionate corn straw for the co-production of XOS, ethanol, and lignin.

Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.

BACKGROUND: Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. METHODS: A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. RESULTS: Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LIMITATIONS: The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. CONCLUSIONS: Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

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.