Urinary Excretion of N1-Methylnicotinamide and N1-Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients.

It is unclear whether niacin nutritional status is a target for improvement of long-term outcome after renal transplantation. The 24-h urinary excretion of N1-methylnicotinamide (N1-MN), as a biomarker of niacin status, has previously been shown to be negatively associated with premature mortality in kidney transplant recipients (KTR). However, recent evidence implies higher enzymatic conversion of N1-MN to N1-methyl-2-pyridone-5-carboxamide (2Py) in KTR, therefore the need exists for interpretation of both N1-MN and 2Py excretion for niacin status assessment. We assessed niacin status by means of the 24-h urinary excretion of the sum of N1-MN and 2Py (N1-MN + 2Py), and its associations with risk of premature mortality in KTR. N1-MN + 2Py excretion was measured in a longitudinal cohort of 660 KTR with LS-MS/MS. Prospective associations of N1-MN + 2Py excretion were investigated with Cox regression analyses. Median N1-MN + 2Py excretion was 198.3 (155.9-269.4) µmol/day. During follow-up of 5.4 (4.7-6.1) years, 143 KTR died, of whom 40 due to an infectious disease. N1-MN + 2Py excretion was negatively associated with risk of all-cause mortality (HR 0.61; 95% CI 0.47-0.79; p < 0.001), and infectious mortality specifically (HR 0.47; 95% CI 0.29-0.75; p = 0.002), independent of potential confounders. Secondary analyses showed effect modification of hs-CRP on the negative prospective association of N1-MN + 2Py excretion, and sensitivity analyses showed negative and independent associations of N1-MN and 2Py excretion with risk of all-cause mortality separately. These findings add further evidence to niacin status as a target for nutritional strategies for improvement of long-term outcome in KTR.

A Noninvasive Urine Metabolome Panel as Potential Biomarkers for Diagnosis of T Cell-Mediated Renal Transplant Rejection.

Acute T cell-mediated rejection (TCMR) is a major complication after renal transplantation. TCMR diagnosis is very challenging and currently depends on invasive renal biopsy and nonspecific markers such as serum creatinine. A noninvasive metabolomics panel could allow early diagnosis and improved accuracy and specificity. We report, in this study, on urine metabolome changes in renal transplant recipients diagnosed with TCMR, with a view to future metabolomics-based diagnostics in transplant medicine. We performed urine metabolomic analyses in three study groups: (1) 7 kidney transplant recipients with acute TCMR, (2) 15 kidney transplant recipients without rejection but with impaired kidney function, and (3) 6 kidney transplant recipients with stable renal function, using 1H-nuclear magnetic resonance. Multivariate modeling of metabolites suggested a diagnostic panel where the diagnostic accuracy of each metabolite was calculated by receiver operating characteristic curve analysis. The impaired metabolic pathways associated with TCMR were identified by pathway analysis. In all, a panel of nine differential metabolites encompassing nicotinamide adenine dinucleotide, 1-methylnicotinamide, cholesterol sulfate, gamma-aminobutyric acid (GABA), nicotinic acid, nicotinamide adenine dinucleotide phosphate, proline, spermidine, and alpha-hydroxyhippuric acid were identified as novel potential metabolite biomarkers of TCMR. Proline, spermidine, and GABA had the highest area under the curve (>0.7) and were overrepresented in the TCMR group. Nicotinate and nicotinamide metabolism was the most important pathway in TCMR. These findings call for clinical validation in larger study samples and suggest that urinary metabolomics warrants future consideration as a noninvasive research tool for TCMR diagnostic innovation.

Correlation Between First Morning Single Void and 24-Hour Urines: The Reliability to Quantify Niacin Status.

BACKGROUND The current common practice when using urine as a biomarker for vitamin excretion is to use a 24-hour sample for analysis. Due to the difficulty involved in this process, we attempted to find an alternative solution through the use of a single first morning void. The aim of our study was to investigate if there is a correlation between the first morning single void and the 24-hour collections of urines for the urine metabolite of niacin, N-1-methylnicotinamide (N1MN), and to test the reliability of utilizing a method using first morning single void collections corrected with the concentration of urine creatinine. MATERIAL AND METHODS All urine samples were collected from 30 healthy adult volunteers over the age of 18 years: 20 females and 10 males. Samples were collected after discarding the first morning urine and collecting every other urine voided during the next 24 hours including the first morning urine of the day after in 2 separate vessels. We analyzed the concentration of N1MN by high performance liquid chromatography and the concentration of creatinine by a commercial kit by spectrophotometry. The B3 excretion was expressed as the ratio of N1MN to creatinine. RESULTS We found a significant correlation between the ratios of first morning single void and 24-hour urines. When comparing males and females, the ratio demonstrated a significant correlation as well. CONCLUSIONS Our results demonstrated that it is possible to substitute a 24-hour collection with a first morning single void urine for the estimation of N1MN excretion.

Urinary Excretion of Niacin Metabolites in Humans After Coffee Consumption.

SCOPE: Coffee is a major natural source of niacin in the human diet, as it is formed during coffee roasting from the alkaloid trigonelline. The intention of our study was to monitor the urinary excretion of niacin metabolites after coffee consumption under controlled diet. METHODS AND RESULTS: We performed a 4-day human intervention study on the excretion of major niacin metabolites in the urine of volunteers after ingestion of 500 mL regular coffee containing 34.8 µmol nicotinic acid (NA) and 0.58 µmol nicotinamide (NAM). In addition to NA and NAM, the metabolites N1 -methylnicotinamide (NMNAM), N1 -methyl-2-pyridone-5-carboxamide (2-Py), and nicotinuric acid (NUA) were identified and quantified in the collected urine samples by stable isotope dilution analysis (SIVA) using HPLC-ESI-MS/MS. Rapid urinary excretion was observed for the main metabolites (NA, NAM, NMNAM, and 2-Py), with tmax values within the first hour after ingestion. NUA appeared in traces even more rapidly. In sum, 972 nmol h-1 of NA, NAM, NMNAM, and 2-Py were excreted within 12 h after coffee consumption, corresponding to 6% of the ingested NA and NAM. CONCLUSION: The results indicate regular coffee consumption to be a source of niacin in human diet.

Use of Polymer Inclusion Membranes (PIMs) as support for electromembrane extraction of non-steroidal anti-inflammatory drugs and highly polar acidic drugs.

The use of polymer inclusion membranes (PIMs) as support of 1-octanol liquid membrane in electromembrane extraction (EME) procedure is proposed. Synthesis of PIMs were optimized to a composition of 29% (w/w) of cellulose triacetate as base polymer and 71% (w/w) of Aliquat®336 as cationic carrier. Flat PIMs of 25µm thickness and 6mm diameter were used. EME protocol was implemented for the simultaneous extraction of four non-steroidal anti-inflammatory drugs (NSAIDs) (salicylic acid, ketoprofen, naproxen and ibuprofen) and four highly polar acidic drugs (anthranilic acid, nicotinic acid, amoxicillin and hippuric acid). Posterior HPLC separation of the extracted analytes was developed with diode array detection. Recoveries in the 81-34% range were obtained. EME procedure was applied to human urine samples.

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes.

Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 induce different age-related metabolic profiles revealed by 1H-NMR spectroscopy in urine and feces of mice.

Age-related dysbioses of intestinal microbiota and decline in the overall metabolic homeostasis are frequently found in the elderly. Probiotic supplementation may represent a way to prevent or reduce the senescence-associated metabolic disorders. The present study evaluated the metabolic impact of Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 supplementation in relation to age by analyzing urine and feces metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy and multivariate analysis. Adult (3 mo old) and aged (16 mo old) mice received an oral supplementation of the 2 probiotics (1 × 10(9) colony-forming units/d each) or phosphate buffered saline (control) daily for 30 d. Urine and feces were collected for 48 h before the end of the study. Partial least squares-discriminant analysis showed that the urinary discriminant metabolites for the probiotic treatment included higher dimethylglycine in adult and aged mice, lower sarcosine and nicotinate in adult mice, higher N-methylnicotinamide in adult mice and lower N-methylnicotinamide in aged mice compared with their controls. These results indicate a probiotic-induced modulation of homocysteine and NAD metabolism pathways, which have important implications because these pathways are involved in essential cellular processes that can be altered in senescence. The probiotic supplementation also modified the fecal metabolic profiles, inducing in both adult and aged mice higher 4-hydroxyphenylacetate and lower xylose in treated mice compared with their control mice, whereas valerate was greater in treated adult mice and lower in treated aged mice compared with their controls. The ANOVA simultaneous component analysis on urinary and fecal metabolic profiling showed an age × treatment interaction (P < 0.05), confirming the age-related modulation of the metabolic response to probiotic supplementation. The results suggest that L. acidophilus and B. lactis may prevent or reduce age-related metabolic dysfunction.

[Investigation of vitamin B1, vitamin B2 and niacin levels among children aged 0-3 years old in Chinese urban and rural areas].

OBJECTIVE: To study the nutritional status and differences in vitamin B1, vitamin B2, and niacin of the urban/rural infants in Shandong Province, and to provide scientific basis for infants nutrition interventions. METHODS: 106 urban infants and 290 rural infants were selected from a city in Shandong Province. Forty milliliter urinary was collected from each one, which was adjusted to pH 4-5 with concentrated hydrochloric acid immediately. The concentration of thiamine, riboflavin and niacin in the urine was detected by fluorescence method. RESULTS: The insufficient percentages of vitamin B, vitamin B2 and niacin in urban infants were 1.9%, 8.0% and 9.1%, and that in rural infants were 4.5%, 56.7% and 27.1%. The median concentrations of vitamin B1 in urban and rural infants were 495.00 and 420.56 microg/g respectively, in which the 12-month and 24-month groups in urban were higher than that in rural (P<0.05). The medians of vitamin B2 content in urban and rural infants were 303.07 and 70.88 microg/g, and the content of vitamin B2 in urban infants was higher than that in rural infants in each group (P<0.05). The median concentrations of niacin content in urban and rural infants were 6.31 and 4.22 microg/g, and the niacin content of 6month-, 12 month-, 18 month- and 24 month- groups in urban infants were higher than that in rural infants (P<0.05). CONCLUSION: There were significant differences in vitamin B1, B2 and niacin content of infants between urban and rural areas, and the nutriture of urban infants was better than the rural infants. More improvement measures should be given to infants in rural areas for the high proportion of vitamin B, and niacin deficiency.

Metabolomic profiling of urine: response to a randomised, controlled feeding study of select fruits and vegetables, and application to an observational study.

Metabolomic profiles were used to characterise the effects of consuming a high-phytochemical diet compared with a diet devoid of fruits and vegetables (F&V) in a randomised trial and cross-sectional study. In the trial, 8 h fasting urine from healthy men (n 5) and women (n 5) was collected after a 2-week randomised, controlled trial of two diet periods: a diet rich in cruciferous vegetables, citrus and soya (F&V), and a fruit- and vegetable-free (basal) diet. Among the ions found to differentiate the diets, 176 were putatively annotated with compound identifications, with forty-six supported by MS/MS fragment evidence. Metabolites more abundant in the F&V diet included markers of the dietary intervention (e.g. crucifers, citrus and soya), fatty acids and niacin metabolites. Ions more abundant in the basal diet included riboflavin, several acylcarnitines and amino acid metabolites. In the cross-sectional study, we compared the participants based on the tertiles of crucifers, citrus and soya from 3 d food records (n 36) and FFQ (n 57); intake was separately divided into the tertiles of total fruit and vegetable intake for FFQ. As a group, ions individually differential between the experimental diets differentiated the observational study participants. However, only four ions were significant individually, differentiating the third v. first tertile of crucifer, citrus and soya intake based on 3 d food records. One of these ions was putatively annotated: proline betaine, a marker of citrus consumption. There were no ions significantly distinguishing tertiles by FFQ. The metabolomic assessment of controlled dietary interventions provides a more accurate and stronger characterisation of the diet than observational data.

Effect of graded levels of niacin supplementation of a semipurified diet on energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin metabolite excretion by growing swine.

Thirty-six crossbred barrows with an average initial age of 42 d and BW of 13.8 kg were placed in individual metabolism crates in a 35-d experiment to evaluate the supplementation of a semipurified diet with graded levels of crystalline niacin. Response criteria were energy and N balance, growth performance, occurrence of niacin deficiency diarrhea, and urinary excretion of the niacin metabolite N(1)-methyl-2-pyridone-5-carboxylamide (PYR). The basal diet met the true ileal Trp requirement of growing swine, and supplementation with 6, 10, 14, 18, 22, or 44 mg of niacin/kg made 6 treatments. Pigs were observed for scours twice daily, and pig BW and feed consumption were determined weekly. Total urine collections and fecal grab samples were made twice daily from each pig from d 28 to 35. Pigs fed the diet containing 14 mg of niacin/kg absorbed and retained more (P < 0.05) grams of N/d, had a greater N digestibility (%, P < 0.05), a greater ADFI and ADG (P < 0.10), and no diarrhea (P < 0.05) compared with pigs fed the diet containing 6 mg of niacin/kg, and pigs fed the diet containing 10 mg of niacin/kg were intermediate in ADG. There were no additional improvements in the response criteria with niacin supplementation greater than 14 mg/kg. Urinary PYR criteria (mg/L and mg/d) were greater (P < 0.001) for pigs fed the diet containing 44 mg of niacin/kg than for pigs fed the diets containing 6 to 22 mg of niacin/kg. However, urinary PYR criteria for pigs fed the diets containing 6 to 22 mg of niacin/kg did not differ from each other, indicating that PYR was not a sensitive indicator of niacin status for growing swine. Niacin treatment did not affect the percentages of N retained/N absorbed, N retained/N intake, DE, or ME. In conclusion, 14 mg of crystalline niacin/kg of semipurified diet adequate in Trp was the minimum concentration of niacin that maximized N utilization and growth performance, and prevented niacin deficiency diarrhea of growing swine in the current experiment. Because practical feed ingredients may be sources of available endogenous niacin, supplementation of practical diets with 100% of the current NRC requirement for niacin should provide adequate niacin for growing swine.

Quantitative determination of nicotinic acid in micro liter volume of urine sample by drop-to-drop solvent microextraction coupled to matrix assisted laser desorption/ionization mass spectrometry.

Drop-to-drop solvent microextraction (DDSME) coupled with matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) for quantitative determination of nicotinic acid in one drop of urine sample has been proposed. All parameters, such as type of organic solvent, extraction time, exposure volume solvent, pH of the sample solution that affecting the separation and preconcentration of nicotinic acid were investigated. Under the optimal conditions, the detection limit of the method was 20 ng mL(-1) and the relative standard deviations (RSD) for determination of the nicotinic acid were in the range of 8.0-12.5%. The calculated calibration curves gave linearity in the range of 80-1000 ng mL(-1). The main advantages of the proposed method are simple, fast, and small amount of sample solution is used for separation and preconcentration of nicotinic acid. This method could be also useful for the analysis of other interested analytes in small volume of biological samples, like plasma, saliva and urine, where the availability of samples are limited.

Urinary excretion of vitamin B1, B2, B6, niacin, pantothenic acid, folate, and vitamin C correlates with dietary intakes of free-living elderly, female Japanese.

We hypothesized that 24-hour urinary excretion of water-soluble vitamins might correlate with their intake in free-living Japanese elderly females aged 70 to 84 years. We performed a cross-sectional study composed of 37 healthy, elderly, Japanese females living freely. All foods and the corresponding weights consumed for 4 consecutive days were recorded accurately. A 24-hour urine sample was collected on the fourth day, and the urinary content of water-soluble vitamins was measured. The urinary levels of all vitamins, except for B(12) (r = 0.01; P = .936), were correlated positively with the mean intake over the recent 4 days (vitamin B1: r = 0.62; P < .001; vitamin B2: r = 0.57; P < .001; vitamin B6: r = 0.37; P < .005; niacin: r = 0.54; P < .001; niacin equivalents: r = 0.54; P < .001; pantothenic acid: r = 0.59; P < .001; folate: r = 0.55; P = .001; and vitamin C: r = 0.53; P < .001). Mean estimated intakes of water-soluble vitamins calculated using urinary concentrations and recovery rates showed 96% to 107% of their 3-day mean intake, except for vitamin B12 (65%). We conclude that urinary levels of water-soluble vitamins, except for B12, reflected their recent intake in free-living Japanese elderly females and could be used as a measure of their intake during the previous few days both for group means and for individual rankings within a group.

A comparison of the pharmacokinetics of two different formulations of extended-release niacin.

OBJECTIVE: The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated) and niacin extended-release caplet formation (NER coated). RESEARCH DESIGN AND METHODS: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 x 1000 mg or 2 x 500 mg tablets. Similarity of NER coated 1 x 1000 mg and NER uncoated 2 x 500 mg was declared if 90% confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) Cmax fell within the pre-specified bounds of [0.7, 1.43]. RESULTS: The GMRs for NUA Cmax demonstrated similarity in the pharmacokinetics of NER uncoated 2 x 500 mg, NER coated 1 x 1000 mg, and NER coated 2 x 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., Cmax of plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA Cmax for NER uncoated 1 x 1000 mg was approximately 40% higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments. CONCLUSION: The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 x 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 x 1000 mg.

A liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomic approach reveals new metabolic effects of catechin in rats fed high-fat diets.

Unbalanced diets generate oxidative stress commonly associated with the development of diabetes, atherosclerosis, obesity and cancer. Dietary flavonoids have antioxidant properties and may limit this stress and reduce the risk of these diseases. We used a metabolomic approach to study the influence of catechin, a common flavonoid naturally occurring in various fruits, wine or chocolate, on the metabolic changes induced by hyperlipidemic diets. Male Wistar rats ( n = 8/group) were fed during 6 weeks normolipidemic (5% w/w) or hyperlipidemic (15 and 25%) diets with or without catechin supplementation (0.2% w/w). Urines were collected at days 17 and 38 and analyzed by reverse-phase liquid chromatography-mass spectrometry (LC-QTOF). Hyperlipidic diets led to a significant increase of oxidative stress in liver and aorta, upon which catechin had no effect. Multivariate analyses (PCA and PLS-DA) of the urine fingerprints allowed discrimination of the different diets. Variables were then classified according to their dependence on lipid and catechin intake (ANOVA). Nine variables were identified as catechin metabolites of tissular or microbial origin. Around 1000 variables were significantly affected by the lipid content of the diet, and 76 were fully reversed by catechin supplementation. Four variables showing an increase in urinary excretion in rats fed the high-fat diets were identified as deoxycytidine, nicotinic acid, dihydroxyquinoline and pipecolinic acid. After catechin supplementation, the excretion of nicotinic acid was fully restored to the level found in the rats fed the low-fat diet. The physiological significance of these metabolic changes is discussed.

The comparative bioavailability of an extended-release niacin and lovastatin fixed dose combination tablet versus extended-release niacin tablet, lovastatin tablet and a combination of extended-release niacin tablet and lovastatin tablet.

Lovastatin and extended-release (ER) niacin in a fixed dose combination (Advicor) is approved for the treatment of dyslipidemia. Since both drugs are extensively metabolized, this study investigated the bioavailability and pharmacokinetics of their co-administration following single-dose administration. In a 4-way crossover study 40 subjects received: two 1000/20 Advicor tablets (ADV), two 1000 mg niacin ER tablets (NSP), two 20mg lovastatin tablets (Mevacor; MEV), and two niacin ER 1000 mg tablets with two lovastatin 20mg tablets (NSP+MEV). Plasma was assayed for niacin, nicotinuric acid (NUA), lovastatin, lovastatin acid and HMGCoA reductase inhibition. Urine was assayed for niacin and its metabolites, NUA, N-methylnicotinamide and N-methyl-2pyridone-5-carboxamide. Least square mean ratios and 90% confidence intervals for C(max) and AUC((0-t)) were determined for NSP+MEV versus MEV or NSP, ADV versus MEV or NSP, and ADV versus NSP+MEV. Co-administration of niacin and lovastatin did not significantly influence C(max) and AUC((0-t)) of lovastatin, niacin, NUA and total urinary recovery of niacin and metabolites. A 22 to 25% decrease in lovastatin acid C(max) was observed while lovastatin acid AUC((0-t)) was not affected. The HMGCoA reductase inhibition C(max) and AUC((0-t)) were not affected indicating that the difference in lovastatin acid C(max) was not clinically relevant.

Low and deficient niacin status and pellagra are endemic in postwar Angola.

BACKGROUND: Outbreaks of pellagra were documented during the civil war in Angola, but no contemporary data on the incidence of pellagra or the prevalence of niacin deficiency were available. OBJECTIVE: The objective was to investigate the incidence of pellagra and the prevalence of niacin deficiency in postwar Angola and their relation with dietary intake, poverty, and anthropometric status. DESIGN: Admissions data from 1999 to 2004 from the pellagra treatment clinic in Kuito, Angola, were analyzed. New patients admitted over 1 wk were examined, and urine and blood samples were collected. A multistage cluster population survey collected data on anthropometric measures, household dietary intakes, socioeconomic status, and clinical signs of pellagra for women and children. Urinary excretion of 1-methylnicotinamide, 1-methyl-2-pyridone-5-carboxymide, and creatinine was measured and hemoglobin concentrations were measured with a portable photometer. RESULTS: The incidence of clinical pellagra has not decreased since the end of the civil war in 2002. Low excretion of niacin metabolites was confirmed in 10 of 11 new clinic patients. Survey data were collected for 723 women aged 15-49 y and for 690 children aged 6-59 mo. Excretion of niacin metabolites was low in 29.4% of the women and 6.0% of the children, and the creatinine-adjusted concentrations were significantly lower in the women than in the children (P < 0.001, t test). In children, niacin status was positively correlated with the household consumption of peanuts (r = 0.374, P = 0.001) and eggs (r = 0.290, P = 0.012) but negatively correlated with socioeconomic status (r = -0.228, P = 0.037). CONCLUSIONS: The expected decrease in pellagra incidence after the end of the civil war has not occurred. The identification of niacin deficiency as a public health problem should refocus attention on this nutritional deficiency in Angola and other areas of Africa where maize is the staple.

Nicotinic acid limitation regulates silencing of Candida adhesins during UTI.

The adherence of Candida glabrata to host cells is mediated, at least in part, by the EPA genes, a family of adhesins encoded at subtelomeric loci, where they are subject to transcriptional silencing. We show that normally silent EPA genes are expressed during murine urinary tract infection (UTI) and that the inducing signal is the limitation of nicotinic acid (NA), a precursor of nicotinamide adenine dinucleotide (NAD+). C. glabrata is an NA auxotroph, and NA-induced EPA expression is likely the result of a reduction in NAD+ availability for the NAD+-dependent histone deacetylase Sir2p. The adaptation of C. glabrata to the host, therefore, involves a loss of metabolic capacity and exploitation of the resulting auxotrophy to signal a particular host environment.

Quantitation of the niacin metabolites 1-methylnicotinamide and l-methyl-2-pyridone-5-carboxamide in random spot urine samples, by ion-pairing reverse-phase HPLC with UV detection, and the implications for the use of spot urine samples in the assessment of niacin status.

A simple ion-pairing reverse-phase HPLC method, with UV diode array detection, was developed and validated for quantitation of the urinary niacin metabolites 1-methylnicotinamide and l-methyl-2-pyridone-5-carboxamide in a single run. Urine samples were purified using a polymer-based mixed mode anion exchange reverse-phase cartridge. Analysis was performed on a reverse-phase C18 column, using a methanol gradient elution system, containing phosphate buffer pH 7.0, 1-heptanesulphonic acid as the ion-pairing agent and trimethylamine as a modifier. The assay was applied to the measurement of the niacin status of two subjects using spot urine samples. The samples were collected over 4 consecutive days and at four time points during 1 day. Status, expressed as the concentration ratios (2-PYR or 1-MN)/creatinine and 2-PYR/l-MN, varied within and between days and was least for fasting samples. This work illustrates the potential of spot urine sampling for niacin status assessment, but highlights the need for further validation prior to its use in field nutritional surveys.