Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomized controlled trials

Objective Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. Methods We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I2 statistic. Results In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I2=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Conclusions Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy

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

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Whole blood NAD and NADP concentrations are not depressed in subjects with clinical pellagra

Population surveys for niacin deficiency are normally based on clinical signs or on biochemical measurements of urinary niacin metabolites. Status may also be determined by measurement of whole blood NAD and NADP concentrations. To compare these methods, whole blood samples and spot urine samples were collected from healthy subjects (n = 2) consuming a western diet, from patients (n = 34) diagnosed with pellagra and attending a pellagra clinic in Kuito (central Angola, where niacin deficiency is endemic), and from female community control subjects (n = 107) who had no clinical signs of pellagra. Whole blood NAD and NADP concentrations were measured by microtiter plate-based enzymatic assays and the niacin urinary metabolites 1-methyl-2-pyridone-5-carboxamide (2-PYR) and 1-methylnicotinamide (1-MN) by HPLC. In healthy volunteers, inter- and intra-day variations for NAD and NADP concentrations were much lower than for the urinary metabolites, suggesting a more stable measure of status. However, whole blood concentrations of NAD and NADP or the NAD:NADP ratio were not significantly depressed in clinical pellagra. In contrast, the concentrations of 2-PYR and 1-MN, expressed relative to either creatinine or osmolality, were lower in pellagra patients and markedly higher following treatment. The use of the combined cut-offs (2-PYR <3.0 micromol/mmol creatinine and 1-MN <1.3 micromol/mmol creatinine) gave a sensitivity of 91% and specificity of 72%. In conclusion, whole blood NAD and NADP concentrations gave an erroneously low estimate of niacin deficiency. In contrast, spot urine sample 2-PYR and 1-MN concentrations, relative to creatinine, were a sensitive and specific measure of deficiency

Influence of dietary niacin on starter pig performance

Two experiments were conducted using 415 weanling pigs (175 in Exp. 1, 240 in Exp. 2) to determine the influence of dietary niacin inclusion on starter pig performance. Pigs were fed a control diet with no added niacin or the control diet with 25, 50, 75 or 100 g/ton of added niacin. From d 0 to 8, increasing dietary niacin increased ADG and ADFI up to 50 g/ton of added niacin. Overall, pigs fed increasing levels of niacin tended to have improved ADG. These results suggest feeding 50 g/ton of added dietary niacin to complex nursery pig diets to improve growth performance

Niacin-induced clotting factor synthesis deficiency with coagulopathy

Although coagulopathy is a well-known complication of severe niacin- induced hepatotoxic reaction, it is not found in patients with minimal aminotransferase level elevations. Three patients with significant clotting factor synthesis deficiency and coagulopathy (prothrombin times, >1.5 times control) from sustained-release niacin had only mild aminotransferase level elevations (1.5 to 2.0 times normal). In each case, protein deficiency, coagulopathy, and aminotransferase level elevation resolved promptly after withdrawal of niacin therapy. In one case, this syndrome recurred after rechallenge with sustained-release niacin, whereas the coagulopathy did not recur in a second patient rechallenged with crystalline niacin. Deficiency in protein synthesis, including coagulation factors, and coagulopathy are unrecognized complications of sustained-release niacin therapy. These cases indicate the need to measure prothrombin times routinely in patients who develop even mild aminotransferase level elevation while receiving sustained- release niacin therapy. These data are important in light of the increasing use of sustained-release niacin in the treatment of patients with lipid disorders

The use of isotopic carbon in a study of the metabolism of anthanilic acid in Neurospora

The finding by Tatum, Banner, and Beadle (l), that the tryptophanless Neurospora mutant strain 10575 accumulates anthranilic acid, which in turn can be utilized for growth of strain 40008, has provided evidence that anthranilic acid is a biochemical precursor of tryptophan in this organism. It has been further established that indole is an intermediate in this conversion (2-5). More recent work with a number of mutants of Neurospora (6-8) has established that tryptophan is a biochemical precursor to niacin with kynurenine and hydroxyanthranilic acid as intermediates. The accumulated evidence has indicated the existence in the mold of the following series of reactions: → Anthranilic acid → indole → tryptophan → kynurenine → 3-hydroxyanthranilic acid → nicotinic acid In the light of this evidence the present work was undertaken to trace the carbon in the carboxyl group of anthranilic acid in order to estimate its contribution as a structural unit in the formation of niacin and tryptophan. The organism chosen for this investigation was a biochemical mutant strain of Neurospora designated as strain 40008. This mutant utilizes anthranilic acid, indole, or tryptophan for growth. The mutant was grown in the presence of anthranilic acid containing Cl4 in the carboxyl group. Niacin and tryptophan were isolated from the mold mycelium and tested for radioactivity

Niacin contents of cereal-milling products in food-composition databases need to be updated

The niacin content of cereal raw materials reported in food-composition databases often differs considerably. One major reason for this discrepancy is the analytical method used for its measurement is that a significant part of the niacin in cereals exists in bound form. In this study, we compared the niacin content of some representative cereal raw materials analysed with a sensitive and validated ultra-high performance liquid chromatography-fluorescence method against the values found in five national food-composition databases. We used established extraction methods that are assumed to liberate niacin available for absorption (acid hydrolysis mimicking human digestion) or total niacin (strong acid-alkaline hydrolysis). The niacin content (mg/100 g dry weight) obtained with acid hydrolysis ranged from a low level in corn flour (0.26), white wheat flour (0.45) and oat flakes (0.48), to a higher level in wholegrain flours (rye: 0.79, barley: 0.99, wheat: 0.88), wheat bran (2.7) and wheat germ (2.7). The niacin content with the acid-alkaline hydrolysis, however, was 1.9-11-fold the value measured after extraction with acid hydrolysis. In general, the niacin content found in the databases is closer to the results obtained after the acid-alkaline extraction, suggesting that the niacin values reported in the databases may not reflect actual bioaccessible niacin but total niacin.Peer reviewe

Established Statin Therapy and the Benefits of Niacin

Residual cardiovascular risk is an issue for patients despite aggressive LDL-C lowering in intervention trials. Currently no guidelines are available for increasing HDL-C, an independent risk factor for coronary vascular disease. Niacin is the most potent drug available for raising plasma levels of HD L-C. A review of literature was conducted to determine if the addition of niacin to an established statin therapy would decrease residual cardiovascular risk. Key words used in multiple literature searches included the terms dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, cardiovascular diseases, niacin, cholesterol HDL, and cardiovascular risk . It has been concluded that niacin is beneficial in reducing coronary artery revascularization, non-fatal MI, strokes and TIA; niacin combined with simvastatin is a better combination choice for increasing HDL and decreasing independent risk factors for CVD; more studies are needed for high risk individuals; and niacin has positive effects on lipid profiles. Future products may become available to combat the number one issue with niacin, flushing. Practitioners should not shy away from using niacin based on the most recent study AIM-HIGH. Educating patients on what to expect when beginnjng niacin therapy is the key to successful treatmen