Niacin Supplementation Research Articles

Effect of Individual or Combination of Dietary Tryptophan and Niacin Supplementation on Productive Performance, Egg Quality, Fatty Liver Incidence, and Serum Measurement of Laying Hens Raised under Heat Stress Conditions

Effect of Individual or Combination of Dietary Tryptophan and Niacin Supplementation on Productive Performance, Egg Quality, Fatty Liver Incidence, and Serum Measurement of Laying Hens Raised under Heat Stress Conditions

P17 Photosensitive rashes in the context of alcoholism: a diagnosis to remember

Abstract Pellagra is a disease defined by a deficiency in niacin and its precursor tryptophan. It is a clinical diagnosis characterized by the ‘four Ds’: dermatitis, dementia, diarrhoea and death (Badawy AA. Pellagra and alcoholism: a biochemical perspective. Alcohol 2014; 49:238–50; Pipili C. The diagnostic importance of photosensitivity dermatoses in chronic alcoholism. Dermatol Online J 2008; 14:15). It is predominantly a disease of non-Western countries with low niacin-containing diets, based on maize, with little meat or vegetables. In Western populations, the commonest causes of pellagra include alcoholism, gut malabsorption, some drugs and, rarely, carcinoid, which causes increased conversion of tryptophan to serotonin, depleting niacin precursor stores. The histopathological features of pellagra are nonspecific; however, pallor and keratinocyte ballooning in the upper third of the epidermis can be suggestive. We present two cases of pellagra in the context of alcoholism. Patient 1 was a 58-year-old woman who presented with a 6-week history of a rash on the dorsal hands which spread to the forearms and dorsum of both feet. Examination revealed a photodistributed erythematous rash with a prominent leading edge, wrinkling and hyperkeratosis. She described loss of appetite, diarrhoea and increasing confusion. A punch biopsy from the right forearm showed focal parakeratosis, perivascular inflammation and mild spongiosis with increased mucin in the superficial dermis. A clinical diagnosis of pellagra was suspected, and empirical niacin was prescribed. Patient 2 was a 60-year-old woman who presented with a 1-month history of a progressive itchy rash affecting her arms and legs. Examination revealed a striking photosensitive erythematous rash of her arms and legs, with complete sparing of the inner aspect of the arms. Skin biopsy showed mild keratosis, with subtle thickening of capillary walls. A diagnosis of pellagra was suspected and treatment with oral niacin commenced. Both patients drank alcohol to excess. Both had negative plasma porphyrins and had not started any new drugs and autoimmune screens were normal. The clinical appearance was identical in both cases. Patient 1 continued to drink excess alcohol, but the rash resolved with niacin supplementation. Patient 2 only took a short course of niacin due to significant flushing, but she managed to reduce her alcohol intake significantly and her rash fully resolved. Pellagra is a rare diagnosis in a Western population, but it is an important diagnosis to remember in patients presenting with a photosensitive rash, particularly in the context of alcohol abuse.

Association of Dietary Niacin Intake with Diabetes in Adults in the United States.

Previous studies have shown inconsistent associations between niacin supplementation and diabetes, and little is known about the relationship between dietary niacin intake and risk of diabetes in the general population. Our study aimed to explore the association between dietary niacin intake and risk of diabetes in the adult population in the United States. Data from the 2005-2016 National Health and Nutrition Examination Surveys were analyzed. Diabetes was diagnosed according to the American Diabetes Association criteria. Multivariate logistic regression models were used to estimate the association between dietary niacin intake and diabetes. Covariates included age, sex, race, family income, educational level, drinking status, smoking status, marital status, and physical activity. This study included 24494 participants of which 13.63% had diabetes. In the fully adjusted model, a high niacin intake was significantly associated with a reduced risk of diabetes in a dose-dependent manner. When extreme quintiles of niacin intake were compared, the multivariable-adjusted OR was 0.66 (95% confidence interval: 0.49, 0.88) for diabetes, and per ten-unit increment in dietary niacin intake was associated with a 14% lower risk of diabetes. When niacin intake was less than 15.01 mg/d, a ten-unit increment in niacin intake was associated with a 24% higher risk of diabetes. However, the effect was not statistically significant. Our results suggest that consumption of adequate amounts of niacin can reduce the risk of diabetes. Furthermore, this protective effect disappeared when the niacin intake was insufficient (less than 15.01 mg/d).

Perspective: Can early embryonic losses be reduced in lactating dairy cows?

Perspective: Can early embryonic losses be reduced in lactating dairy cows?

Nicotinic Acid Catabolism Modulates Bacterial Mycophagy in Burkholderia gladioli Strain NGJ1.

Burkholderia gladioli strain NGJ1 exhibits mycophagous activity on a broad range of fungi, including Rhizoctonia solani, a devastating plant pathogen. Here, we demonstrate that the nicotinic acid (NA) catabolic pathway in NGJ1 is required for mycophagy. NGJ1 is auxotrophic to NA and it potentially senses R. solani as a NA source. Mutation in the nicC and nicX genes involved in NA catabolism renders defects in mycophagy and the mutant bacteria are unable to utilize R. solani extract as the sole nutrient source. As supplementation of NA, but not FA (fumaric acid, the end product of NA catabolism) restores the mycophagous ability of ΔnicC/ΔnicX mutants, we anticipate that NA is not required as a carbon source for the bacterium during mycophagy. Notably, nicR, a MarR-type of transcriptional regulator that functions as a negative regulator of the NA catabolic pathway is upregulated in ΔnicC/ΔnicX mutant and upon NA supplementation the nicR expression is reduced to the basal level in both the mutants. The ΔnicR mutant produces excessive biofilm and is completely defective in swimming motility. On the other hand, ΔnicC/ΔnicX mutants are compromised in swimming motility as well as biofilm formation, potentially due to the upregulation of nicR. Our data suggest that a defect in NA catabolism alters the NA pool in the bacterium and upregulates nicR which in turn suppresses bacterial motility as well as biofilm formation, leading to mycophagy defects. IMPORTANCE Mycophagy is an important trait through which certain bacteria forage over fungal mycelia and utilize fungal biomass as a nutrient source to thrive in hostile environments. The present study emphasizes that nicotinic acid (NA) is important for bacterial motility and biofilm formation during mycophagy by Burkholderia gladioli strain NGJ1. Defects in NA catabolism potentially alter the cellular NA pool, upregulate the expression of nicR, a negative regulator of biofilm, and therefore suppress bacterial motility as well as biofilm formation, leading to mycophagy defects.

The Effect of Zinc and Niacin Powder Addition on some Physiological and Production Performance of Turkey

A study was carried out to look into the effects of dietary zinc and nicotinic acid (niacin) supplementation on growth performance, hematology and biochemical parameters of turkey. The birds were distributed in to four treatments each treatment have three replicates. (3 birds / replicate) T1 no additive as control, fed diets supplemented with Zn (100 mg/kg) T2, Niacin (100 mg/kg diet) T3 and combination of them Zn100 mg/kg+ niacin 100 mg/kg) T4. the results analyzed by CRD arrangement design. Obvious results indicated that supplemented Zn and Niacin enhance the production performance and make a positive effect on the hematology (RBC count, Hb concentration, PCV) and biochemical parameters In each of (AST, ALT, cholesterol and triglyceride

Effects of endophyte-infected tall fescue on performance of genotyped pregnant beef cows supplemented with rumen-protected niacin

A total of 28 Angus × Simmental pregnant dams (11 cows and 17 heifers) were selected based on genetic resistance to fescue toxicosis based on a commercial genetic test (T-snip™, Ag. Botanica, Columbia, MO). Subsequently, dams were divided based on genetic resistance to fescue toxicosis and randomly assigned to dietary treatments: 1) Susceptible Control (SC; n = 7); 2) Susceptible Niacin (SN; n = 7); 3) Tolerant Control (TC; n = 7); and 4) Tolerant Niacin (TN; n = 7). All animals received 1.16 kg of endophyte-infected (E+) tall fescue seeds for a period of 30 days. Ergovaline concentration in fescue seeds was ∼5,000 ppb on a DM basis. Dams in SN and TN groups received 6 g/hd/day as-fed of top-dressed rumen-protected niacin, following manufacturer's maximum dose recommendation. Dams in the TN group experienced an accelerated reduction in BW as compared to the rest of the treatments. However, TN offspring did not show BW differences at birth or weaning as compared to those born to dams in other treatments. Milk production was estimated by the weigh-suckle-weigh method, and no difference was observed among treatments. All dams had a reduction in circulating prolactin concentration, indicating that all animals were experiencing fescue toxicosis. In addition, blood metabolites that indicate liver health status were markedly decreased at the end of the study. Overall, these results suggest that dams receiving E+ tall fescue seeds were effectively exposed to fescue toxicosis symptoms. Nevertheless, neither rumen-protected niacin supplementation nor genetic test for resistance to fescue toxicosis could be used as an efficient mechanism of dampening these symptoms.

Large Supplements of Nicotinic Acid and Nicotinamide Increase Tissue NAD+ and Poly(ADP-Ribose) Levels but Do Not Affect Diethylnitrosamine-Induced Altered Hepatic Foci in Fischer-344 Rats

Poly(ADP-ribose) is a homopolymer of ADP-ribose units synthesized from NAD+ on nuclear acceptor proteins and is known to be involved in DNA repair. It is not known whether large oral doses of the clinically utilized NAD precursors nicotinic acid or nicotinamide affect poly(ADP-ribose) metabolism or the cellular response to DNA damage. In our first study, using Fischer-344 rats, 2 wk of dietary nicotinic acid supplementation (500 and 1000 mg/kg diet) caused elevated levels of NAD+ in the blood, liver, heart and kidney, while nicotinamide caused elevated levels only in the blood and liver, compared with controls fed a diet containing 30 mg/kg nicotinic acid. Both nicotinic acid and nicotinamide, at 1000 mg/kg diet, caused elevations in liver NAD+, by 44 and 43%, respectively. Only nicotinamide, however, elevated liver poly(ADP-ribose) (63% higher than control group). Following treatment with the hepatocarcinogen diethylnitrosamine, higher levels of hepatic NAD+ were observed in rats fed both nicotinic acid and nicotinamide at 1000 mg/kg diet, but only nicotinic acid supplementation caused a greater accumulation of hepatic poly(ADP-ribose) (61% higher than control group). Neither of the dietary treatments significantly affected the proportion of the liver occupied by placental glutathione-S-transferase positive foci. These results show that poly(ADP-ribose) synthesis is not directly responsive to hepatic NAD+ levels during niacin supplementation, and that the mechanisms of action of nicotinic acid and nicotinamide are different. The observed changes in poly(ADP-ribose) metabolism do not appear to cause any change in susceptibility to chemically induced carcinogenesis in this organ.

Quantitative Efficacy of Niacin Sources for Chicks: Nicotinic Acid, Nicotinamide, NAD and Tryptophan

A niacin-deficient diet based upon corn and casein was used to establish growth-promoting efficacy of various sources of niacin activity. In the presence of excess dietary nicotinamide, chicks fed the corn-casein diet achieved maximal weight gain when 100 mg/kg of L-tryptophan was supplemented. The basal diet for efficacy studies therefore contained 100 mg/kg of added tryptophan and no supplemental nicotinic acid. Weight gain in the linear response surface of the growth curve proved to be a far better measure of niacin bioactivity than tissue accumulation of NAD(P). Slope-ratio growth efficacy studies indicated that excess dietary tryptophan was 1.94 +/- 0.14% as efficient as nicotinic acid in furnishing bioavailable niacin activity (52:1, wt:wt). Relative to nicotinic acid used as a standard (100%), nicotinamide bioactivity was 124%. Nicotinamide in NAD was utilized with an efficiency of 95% relative to nicotinamide per se.

Heat ameliorative effects of rumen protected niacin supplementation in lactating Surti buffaloes

Niacin may cause evaporative thermolysis through cutaneous hyperemia, vasodilation, increased sweating rate and decreased skin temperature. It is antilipolytic and can improve metabolic responses. Heat stress ameliorative effects of rumen protected niacin (RPN) supplementation in lactating Surti buffaloes during summer has been investigated in present study. Fourteen lactating Surti buffaloes were divided into two groups (Control-T1, N=7; RPN-T2, N=7). T2 (RPN) group was supplemented with RPN 6 g/ animal/ day in two divided dose for 4 weeks. Meteorological, physiological, sweating rate and skin temperature parameters, milk yield and composition were recorded at weekly intervals. Hematological and biochemical analytes were analyzed at week 1 and 4. RPN supplementation decreased physiological parameters RT, RR and TT; increased (P≤0.05) sweating rate and decreased (P≤0.05) skin surface temperature; increased (P≤0.05) TEC, Hb, HCT, LYM and decreased (P≤0.05) GRAN in hematological profile; increased (P≤0.05) glucose and decreased (P≤0.05) cholesterol, triglyceride, NEFA and BHB among biochemical metabolites and increased (P≤0.05) GSH and SOD and decreased (P≤0.05) LPO in oxidative stress profile. RPN supplementation increased milk yield and milk fat. It was concluded that supplementation of rumen protected niacin in lactating Surti buffaloes increases sweating rate, reduces oxidative stress and increases milk fat and milk production.

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

BackgroundThe 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.MethodsOur 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.ResultsA 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.ConclusionAccording 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.

Alleviation effects of niacin supplementation on beef cattle subjected to heat stress: A metagenomic insight.

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.

Nicotinic acid supplementation contributes to the amelioration of Alzheimer's disease in mouse models.

Alzheimer's disease (AD) is the most common cause of dementia. Effective therapy, early diagnosis, and intervention are still lacking. Non-drug therapy and lifestyle interventions have become important means to prevent the occurrence and progression of AD, with nutritional therapy being one such example. Nutritional therapy, as a non-pharmacological intervention for AD, has made significant progress and shown significant promise for the development of treatment regimens in recent years. Niacin is a critical vitamin available in the forms of nicotinamide (NAM) and nicotinic acid (NA). In tissues, niacin is transformed into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in a variety of cellular processes. Recent researches indicate that niacin may be beneficial in the prevention and treatment of aging, cancer, and metabolic illnesses. To detect the mechanism of affection of niacin in AD, we found out GSE135999 from the Gene Expression Omnibus (GEO) database which is microarray data containing samples of 24 wild-type (WT) and 24 APP/PS1 AD mice, given either nicotinamide riboside (NR; 12 mM) or nothing (CTR) in their drinking water. We conducted a more reliable data analysis method Weighted Gene Co-expression Network Analysis (WGCNA) to confirm the central players (hub genes) and related pathways associated between niacin and AD. To validate the affection of niacin in AD mice, we selected 6 WT and 12 APP/PS1 transgenic mice, the 12 APP/PS1 mice were treated with a niacin acid supplement diet or normal food. Six months later, behavioral tests were performed. Our research revealed the hub genes and pathways involved in the enhancement of cognition in AD animal models with niacin supplementation, through transcriptomics analysis, systems biology technique and in vivo. The hub genes were Ctnnb1, Mdm2, Crebbp, Gnb2l1/RACK1 and Pten. The related pathways were circadian rhythm, ubiquitin-mediated proteolysis, and long-term potentiation. A niacin supplementary diet may be a safe and simple choice for AD prevention and treatment. Niacin can enhance cognitive capacity in AD through a variety of mechanisms, among which Ctnnb1, Mdm2, Crebbp, Gnb2l1/RACK1 and Pten are significant.

Niacin Improves Intestinal Health through Up-Regulation of AQPs Expression Induced by GPR109A.

(1) Background: Changes in the expression of aquaporins (AQPs) in the intestine are proved to be associated with the attenuation of diarrhea. Diarrhea is a severe problem for postweaning piglets. Therefore, this study aimed to investigate whether niacin could alleviate diarrhea in weaned piglets by regulating AQPs expression and the underlying mechanisms; (2) Methods: 72 weaned piglets (Duroc × (Landrace × Yorkshire), 21 d old, 6.60 ± 0.05 kg) were randomly allotted into 3 groups for a 14-day feeding trial. Each treatment group included 6 replicate pens and each pen included 4 barrows (n = 24/treatment). Piglets were fed a basal diet (CON), a basal diet supplemented with 20.4 mg niacin/kg diet (NA) or the basal diet administered an antagonist for the GPR109A receptor (MPN). Additionally, an established porcine intestinal epithelial cell line (IPEC-J2) was used to investigate the protective effects and underlying mechanism of niacin on AQPs expression after Escherichia coli K88 (ETEC K88) treatment; (3) Results: Piglets fed niacin-supplemented diet had significantly decreased diarrhea rate, and increased mRNA and protein level of ZO-1, AQP 1 and AQP 3 in the colon compared with those administered a fed diet supplemented with an antagonist (p < 0.05). In addition, ETEC K88 treatment significantly reduced the cell viability, cell migration, and mRNA and protein expression of AQP1, AQP3, AQP7, AQP9, AQP11, and GPR109A in IPEC-J2 cells (p < 0.05). However, supplementation with niacin significantly prevented the ETEC K88-induced decline in the cell viability, cell migration, and the expression level of AQPs mRNA and protein in IPEC-J2 cells (p < 0.05). Furthermore, siRNA GPR109A knockdown significantly abrogated the protective effect of niacin on ETEC K88-induced cell damage (p < 0.05); (4) Conclusions: Niacin supplementation increased AQPs and ZO-1 expression to reduce diarrhea and intestinal damage through GPR109A pathway in weaned piglets.

Abstract 2970: Oncometabolites confer vulnerabilities in NAD biosynthesis via NAPRT gene silencing

Abstract Cancer associated mutations in citric acid cycle enzymes cause overproduction of 2-hydroxyglutarate (2HG), fumarate, or succinate, commonly referred to as oncometabolites. These oncometabolite producing mutations are prevalent in 70% of gliomas, &amp;gt;76% of hereditary leiomyomatosis and renal cell carcinoma, and &amp;gt;25% of paraganglioma and pheochromocytomas, respectively. These oncometabolite producing cancers harbor vulnerabilities in multiple cellular pathways because oncometabolites competitively inhibit alpha ketoglutarate dependent dioxygenases. This group of enzymes includes the ten eleven translocation (TET) family of enzymes, which catalyze locus specific DNA demethylation. Thus, oncometabolite producing cancers have been shown to exhibit global DNA hypermethylation, which drastically alters gene expression in the cell and is thought to occur via TET inhibition. Cells with isocitrate dehydrogenase 1 (IDH1) mutations, which produce 2HG, have loss of expression of a critical NAD biosynthesis enzyme, nicotinate phosphoribosyltransferase (NAPRT). We show that in addition to IDH1 mutant cells, fumarate hydratase (FH)-deficient isogenic cell lines, which overproduce fumarate, show loss of NAPRT expression, which can be targeted by nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. The goal of our work is to determine if this NAPRT silencing is present in many oncometabolite producing cancers, elucidate the mechanism of silencing, and test therapies to target this vulnerability in NAD biosynthesis. FH-deficient cancer cell lines show reduction of NAPRT mRNA levels by qRT-PCR and absence of protein by western blot, suggesting a reduction in NAPRT transcription. In addition, FH-deficient cell lines exhibit synthetic lethality in short term cell viability assays when treated with NAMPT inhibitor, FK866, which inhibits a parallel NAD biosynthesis pathway. Cell viability is not rescued by nicotinic acid supplementation in FH-deficient lines while parental lines are rescuable, validating the loss of functional NAPRT in only FH-deficient lines. Furthermore, patient samples of FH-deficient renal cell carcinomas show higher NAPRT promoter methylation compared to healthy tissue via methylation array. Ongoing studies are investigating the role of TET1/2/3 enzymes in NAPRT promoter methylation. Together, these results suggest that hypermethylation of the NAPRT promoter is associated with silencing of NAPRT expression in FH-deficient cancers, which can be therapeutically targeted through NAMPT inhibition. Citation Format: Katelyn Noronha, Jiayu Liang, Ranjit Bindra. Oncometabolites confer vulnerabilities in NAD biosynthesis via NAPRT gene silencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2970.

Effect of vitamin blend supplementation on the ingestive, digestive, and ruminal parameters of Nellore cattle

Rumen cannulated Nellore bulls (n = 4) were used in a 4 × 4 Latin square design, with a 2 × 2 factorial scheme to evaluate the effects of vitamin supplementation on: (1) ingestive, digestive, and ruminal parameters; (2) serum concentrations of 25-hydroxyvitamin D (25(OH)D); and (3) in situ degradability of complete diets. The factors consisted of two fat-soluble vitamin blend (ADE) supplementation levels (ADE− or ADE+) and two B vitamin blend (biotin, niacin, and thiamine) supplementation levels (B-blend− or B-blend+). Thus, the treatments evaluated consisted of no vitamin supplementation (ADE− B-blend−), supplementation of a B vitamin blend (ADE− B-blend+), supplementation with a fat-soluble vitamin blend (ADE+ B-blend−), or a combination of these two blends (ADE+ B-blend+). Nutrient intake and DM, as well as ruminal digestibility were not affected (P > 0.05) by any of the vitamin supplementations. The apparent total-tract digestibility of DM, organic matter (OM), neutral detergent fiber corrected for residual ash and protein (apNDF), crude protein (CP), and non-fiber carbohydrates (NFC) were not influenced by the experimental diets (P > 0.05). Furthermore, an increase in starch total-tract digestibility was verified with ADE supplementation in the diets (P = 0.031). None of the in situ parameters were affected (P > 0.05) by vitamin supplementation. Further, the treatments did not affect ruminal kinetics (ki, kp, and kd,) of DM, OM, and starch (P > 0.05). The omasal flow of total N, NH3-N, non-ammonia N, microbial N, and non-ammonia non-microbial N (P > 0.05) or the efficiency of microbial protein synthesis (P > 0.05) were not affected by vitamin blend supplementation. The total fat volatile acid (VFA) concentrations, as well lactate concentration were not affected (P > 0.05) by vitamin blend supplementation. Bulls that consumed the combination of ADE and B-blend supplementation had lower ruminal NH3-N concentrations (P = 0.008). B-blend vitamin supplementation decreased ruminal pH (P = 0.003). As expected, concentrations of serum 25(OH)D increased (P = 0.001) in Nellore bulls fed diets with the combination of fat-soluble vitamin (ADE) and B-blend supplementation. Supplementing Nellore bulls with a vitamin blend containing 25(OH)D3 was a successful strategy for increasing circulating concentrations of 25(OH)D. The B vitamin blend (biotin, niacin, and thiamine) supplementation did not improve ruminal fermentation, ingestive or digestive parameters. However, the fat-soluble vitamin blend (ADE) supplementation increased total-tract starch digestibility.

Effect of different dosages of sodium butyrate and niacin on growth, faecal microbiota and Vitamin B metabolism in weaned piglets.

Our study aimed to evaluate the effects of different dosages of sodium butyrate and niacin on the growth performance, faecal Vitamin B and microbiota in weaned piglets. Seventy-two weaned piglets (Duroc × Landrace × Yorkshire, age of 21 days) were randomly assigned to one of six treatments (12 pigs/treatment); the control (CT) group was administered a basal diet. The groups in which concentration ratios of sodium butyrate to niacin were 100: 1, 100: 2, 100: 4, 100: 8 and 100: 16 (BN1, BN2, BN4, BN8 and BN16) were administered a basal diet supplemented with 2000 mg kg-1 sodium butyrate and 20, 40, 80, 160 or 320 mg·kg-1 niacin. After 14-day treatment, the samples were collected. The results showed that feed conversion rate (FCR) was reduced and average daily gain (ADG) was increased in BN2 (p < 0.05). The diarrhoea index of pigs decreased with the low supplement. Additionally, compared with the CT group, other groups significantly increased (p < 0.05) the abundance of Firmicutes (BN4, phylum), Lactobacillaceae (BN8, family), Megasphaera (BN8, genus) and Lactobacillus (BN8, genus). Furthermore, the sodium butyrate and niacin supplementation influence Vitamin B1, Vitamin B2, pyridoxine, niacin, nicotinamide and Vitamin B12 (p < 0.05). Correlation analysis of the association of micro-organisms with Vitamin B indicated that changes of Vitamin B metabolism have a potential correlation with alterations of faecal microbiota in weaned piglets. The results indicated that adding sodium butyrate and niacin in the diet could promote the performance and improve the faecal microbiota and Vitamin B metabolism in weaned piglets. Our study might provide clues to the research of correlations between faecal bacteria and faecal Vitamin B, and these findings will contribute to the direction of future research in weaned piglets.

NAXE deficiency: A neurometabolic disorder of NAD(P)HX repair amenable for metabolic correction.

The NAD(P)HX repair system is a metabolite damage repair mechanism responsible for restoration of NADH and NADPH after their inactivation by hydration. Deficiency in either of its two enzymes, NAD(P)HX dehydratase (NAXD) or NAD(P)HX epimerase (NAXE), causes a fatal neurometabolic disorder characterized by decompensations precipitated by inflammatory stress. Clinical findings include rapidly progressive muscle weakness, ataxia, ophthalmoplegia, and motor and cognitive regression, while neuroimaging abnormalities are subtle or nonspecific, making a clinical diagnosis challenging. During stress, nonenzymatic conversion of NAD(P)H to NAD(P)HX increases, and in the absence of repair, NAD(P)H is depleted, and NAD(P)HX accumulates, leading to decompensation; however, the contribution of each to the metabolic derangement is not established. Herein, we summarize the clinical knowledge of NAXE deficiency from 30 cases and lessons learned about disease pathogenesis from cell cultures and model organisms and describe a metabolomics signature obtained by untargeted metabolomics analysis in one case at the time of crisis and after initiation of treatment. Overall, biochemical findings support a model of acute depletion of NAD+, signs of mitochondrial dysfunction, and altered lipidomics. These findings are further substantiated by untargeted metabolomics six months post-crisis showing that niacin supplementation reverses primary metabolomic abnormalities concurrent with improved clinical status.

NAD+ precursor concentrations are elevated in the follicular fluid of mares following oral supplementation of nicotinic acid

Niacin deficiency has recently been associated with congenital malformations in humans and embryonic death and resorption in mice (Shi et al. New England Journal of Medicine. 2017; 377(6):544-552). Mares suffer from high rates of early embryonic loss (Newcombe. Equine Veterinary Education. 12(2):88-101), the aetiology of which remains unknown. Increasing the levels of nicotinamide adenine dinucleotide (NAD+) through supplementing NAD+ precursors has resulted in an improvement in oocyte quality in mice (Bertoldo et al. Cell Rep. 2020; 30: 1670-1681). However, little is known regarding the requirement of niacin and NAD+ in reproductive processes in the mare. The aim of this study was to determine the effect of oral nicotinic acid (NA) supplements, a form of niacin, on the composition of nicotinamide adenine dinucleotide (NAD+) metabolites in the blood and follicular fluid of mares. Vehicle alone or NA (3 g per os) was administered to 7 mares over a minimum of 3 consecutive days during the oestrous cycle. Blood samples were collected immediately prior tosupplemental feeding and at follicular fluid aspiration. Follicular fluid was collected from the dominant follicle through transvaginal ultrasound guided aspiration. Blood and follicular fluid samples were processed and analysed by mass spectrometry. The concentration of nicotinamide mononucleotide (NMN) in the follicular fluid of NA-fed mares was greater than that in the corresponding plasma (15.0 ± 6.5 vs. 3.3 ± 0.9 ng/µL; p < 0.05) and in the follicular fluid of vehicle-fed mares (1.5 ± 0.5 ng/µL; p < 0.001). Meanwhile, the concentration of NA, nicotinamide (NAM) and nicotinuric acid (NUR) tended to be greater in the follicular fluid of NA supplemented mares (1043.9 ± 953.5, 1641.7 ± 256.1 and 5.5 ± 5.1 ng/µL) than in the corresponding plasma (70.8 ± 15.4, 875.6 ± 361.1 and 0.6 ± 0.2, respectively; p < 0.1). The results show that NA supplementation increased the bioavailability of NAD+ precursors in the follicular fluid of the dominant follicle, which is proposed to better promote the maturation of good quality oocytes, especially in older mares.

Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice.

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice.