Nicotinic Acid Group Research Articles

Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males

Abstract Objectives To examine the effect of the NAD+ precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people. Methods In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65–75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured. Results Resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD+-specific pathways (e.g., de novo NAD+ biosynthetic processes) and genes (e.g., NADSYN1) were uniquely regulated by NA. Conclusions NA might be an effective strategy for improving ageing muscle mitochondrial health.

Dietary nicotinic acid promotes the growth and tryptophan metabolome of Chinese mitten crab (Eriocheir sinensis) through ACMSD and NADs

This paper did research on the effect of dietary nicotinic acid (NA) on lipid metabolism and tryptophan metabolome of Chinese mitten crab (Eriocheir sinensis) to promote its growth. Three diets to administer to E. sinensis (37.25 ± 0.5 g), respectively, for 10 weeks were designed to contain 0% NA (control), 0.02% NA, and 0.10% NA. According to the results, when feeding crabs with 0.02% NA diet, the specific growth rate (SGR) increased markedly while the feed conversion ratio (FCR) was the opposite compared with 0% NA group. The content of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL) in hemolymph decreased significantly when feeding crabs with 0.02% NA diet while the content of high-density lipoprotein cholesterol (HDL) was the opposite. In addition, the relative expression level of microsomal triglyceride transfer protein (mttp) and kynureninase (KFase) decreased significantly in 0.10% NA group while the relative expression level of sterol regulatory element-binding protein 1 (srebp-1) and nicotinamide adenine dinucleotide synthetase (NADs) increased significantly in 0.02% NA group. Meanwhile, the protein expression of 2-amino-3-carboxymuconic semialdehyde decarboxylase (ACMSD) in 0.02% NA group had a very significant increase compared with the other two groups. The result of tryptophan metabolome in hepatopancreas indicates that 0.02% NA in the diet could inhibit the downstream metabolic pathway of tryptophan. According to the results of this research, 0.02% NA in the diet can improve the growth and tryptophan metabolome through ACMSD and NADs, and lipid metabolism is also improved in this group, while 0.10% NA in the diet has no effect on crabs in growth performance.

Nicotinic Acid Improves Endurance Performance of Mice Subjected to Treadmill Exercise

Recently, administration of nicotinic acid (NA) at a pharmacological dose was found to induce a similar change in the muscle´s contractile and metabolic phenotype as observed in response to endurance exercise. Thus, the hypothesis was tested that combined NA administration and endurance exercise promotes the adaptation of muscle to regular exercise and improves the endurance performance to a greater extent than exercise alone. Thus, 30 adult mice were randomly divided into three groups of 10 mice/group. The control and the exercise (EX) group received an adequate NA diet, while the EX + NA group received a high NA diet. Mice of the EX and the EX + NA group were subjected to a treadmill endurance exercise program five times/week during the experimental period of 42 days. At day 41, endurance performance was greater in the EX + NA group than in the control and the EX group (p < 0.05). Mice of the EX + NA group had a higher type IIA (+60%) and a lower type IIB (−55%) fiber percentage in gastrocnemius (GN) muscle than control mice (p < 0.05), while the type I fiber percentage in GN muscle tended to be increased (+100%) in the EX + NA group compared to the control group (p = 0.051). In the EX + NA group, glycogen concentration (+15%) and mRNA levels of two glycolytic (+70–80%) and two glycogenolytic enzymes (+80–120%) in GN muscle were increased compared to the control group (p < 0.05). In conclusion, feeding a high NA diet induces changes in skeletal muscle fiber composition and improves endurance performance of mice subjected to regular endurance exercise.

Effect of in ovo Injection of Nicotonic Acid, Pantothenic Acid or Folic Acid on Immune System and Growth of Broiler Chickens

BACKGROUND: In ovo injection of nutrients as an early feeding method in birds directly supplies the nu- trients to the developing embryo. OBJECTIVES: This study was designed to evaluate the effects of in ovo injection of nicotonic acid, panto- thenic acid and folic acid on the performance and immune system of broilers. METHODS: 450 Ross 308 fertile eggs were divided into 5 groups and placed in a hatchery machine. Five experimental groups included in ovo injection of 0.121 mg of nicotonic acid, 0.052 mg of pantothenic acid, 0.007 mg of folic acid on the 14th day of incubation period, positive control or injection control (physiological serum injection) and negative control (non injecting control). RESULTS: At the age of 18 days of the rearing period, injection of pantothenic acid and nicotinic acid in- creased the antibody titre against Newcastle Virus and folic acid and pantothenic acid reduced the SRBC titer. At 35 days of age, nicotinic acid and folic acid had lower SRBC titer than the negative control group. The highest lymphocyte to heterophilia ratio was observed in the pantothenic acid group and the lowest levels were seen in the folic acid group. In ovo injection of nicotinic acid and pantothenic acid caused weight loss in chicks during the first and second weeks of rearing period compared to positive and negative controls groups. CONCLUSIONS: The results of this study indicated a positive effect of in ovo injection of pantothenic acid and nichotinic acid on some immune parameters of broiler chicks. In despite of the negative effect of in ovo injection of nicotinic acid and pantothenic acid on growth rate of chicks during the first and second week of age, there was a compensatory growth for the nicotinic acid group such that this treatment positively influenced the final weight of the broilers.

Uncovering the mechanism whereby dietary nicotinic acid increases the intramuscular fat content in finishing steers by RNA sequencing analysis

In our previous study, we found that a higher dosage of nicotinic acid (NA) in the diet dramatically increases intramuscular fat (IMF) content and improves meat quality in finishing steers. We hypothesised that increased IMF results from the regulation of genes associated with adipogenesis. To address this hypothesis, RNA-seq was used to investigate gene-expression profiles of longissimus muscles from the same 16 cattle that were also used in our previous study and treated with or without dietary NA. Four cDNA libraries were constructed and sequenced. The repeatability and reproducibility of RNA-seq data were confirmed by quantitative reverse-transcription polymerase-chain reaction. In total, 123 differentially expressed genes (DEGs) were identified between longissimus muscles treated and those not treated with dietary NA. Of the 123 DEGs, 117 genes were upregulated by the NA treatment. These DEGs were enriched in 21 pathways, including the extracellular matrix (ECM) –receptor interaction, PPAR signalling pathway, adipocytokine signalling pathway and transforming growth factor-β signalling pathway, all of which are associated with lipid metabolism. Furthermore, candidate genes related to adipocyte differentiation and adipogenesis (PLIN1, PLIN2, ADPN, LEP, LCN2 and SOCS3), lipid metabolism (FABP4, RBP4, GAL, ANXA1, ANXA2 and PTX3) and fatty acid synthesis and esterification (ELOVL6, ACSM1, SOT1 and PTGIS) were upregulated in the NA group. Three genes involved in glucose metabolism (PGAM1, UGDH and GLUT3) were also transcriptionally upregulated. However, MYH4 that encodes glycolytic Type IIb muscle fibres was downregulated by dietary NA. These gene expression results indicated a confirmation of our hypothesis that dietary NA increases the IMF content of longissimus muscle through upregulating the expression of the genes related to adipocyte differentiation, adipogenesis and lipid and glucose metabolism.

Effects of supplementing rumen-protected niacin on fiber composition and metabolism of skeletal muscle in dairy cows during early lactation

Nicotinic acid (NA) has been shown to induce muscle fiber switching toward oxidative type I fibers and a muscle metabolic phenotype that favors fatty acid (FA) utilization in growing rats, pigs, and lambs. The hypothesis of the present study was that supplementation of NA in cows during the periparturient phase also induces muscle fiber switching from type II to type I fibers in skeletal muscle and increases the capacity of the muscle to use free FA, which may help to reduce nonesterified fatty acid (NEFA) flow to the liver, liver triglyceride (TG) accumulation, and ketogenesis. Thirty multiparous Holstein dairy cows were allocated to 2 groups and fed a total mixed ration without (control group) or with ∼55 g of rumen-protected NA per cow per day (NA group) from 21 d before expected calving until 3 wk postpartum (p.p.). Blood samples were collected on d -21, -14, -7, 7, 14, 21, 35, and 63 relative to parturition for analysis of TG, NEFA, and β-hydroxybutyrate. Muscle and liver biopsies were collected on d 7 and 21 for gene expression analysis and to determine muscle fiber composition in the musculus semitendinosus, semimembranosus, and longissimus lumborum by immunohistochemistry, and liver TG concentrations. Supplementation of NA did not affect the proportions of type I (oxidative) or the type II:type I ratio in the 3 muscles considered. A slight shift from glycolytic IIx fibers toward oxidative-glycolytic fast-twitch IIa fibers was found in the semitendinosus, and a tendency in the longissimus lumborum, but not in the semimembranosus. The transcript levels of the genes encoding the muscle fiber type isoforms and involved in FA uptake and oxidation, carnitine transport, tricarboxylic acid cycle, oxidative phosphorylation, and glucose utilization were largely unaffected by NA supplementation in all 3 muscles. Supplementation of NA had no effect on plasma TG and NEFA concentrations, liver TG concentrations, and hepatic expression of genes involved in hepatic FA utilization and lipogenesis. However, it reduced plasma β-hydroxybutyrate concentrations in wk 2 and 3 p.p. by 18 and 26% and reduced hepatic gene expression of fibroblast growth factor 21, a stress hormone involved in the regulation of ketogenesis, by 74 and 56%. In conclusion, a high dosage of rumen-protected NA reduced plasma β-hydroxybutyrate concentrations in cows during early lactation, but failed to cause an alteration in muscle fiber composition and muscle metabolic phenotype.

INFLUENCE OF NICOTINIC ACID ON SUBFRACTIONAL SPECTRUM OF LOW, INTERMEDIATE AND HIGH DENSITY LIPOPROTEINS IN PATIENTS WITH HYPERLIPOPROTEINEMIA(а)

Aim. To evaluate the influence of nicotinic acid (NA) on subfractional spectrum of proand antiatherogenic lipoproteides in hyperlipoproteidemia (a) patients. Material and methods . Totally, 78 patients included, with Lp(a) level more than 20 mg/dL, taking either combinational statin and NA therapy (n=43), or on monotherapy by statins (n=13), or monotherapy by NA (n=22). Lipid profile parameters were analyzed with the assays “Biocon/Analyticon” (Germany), quantitative subfractional contents were assessed with the system Lipoprint® (Quantimetrix,USA), Lp(a) concentriation — with immune enzyme assay. Results. Results. In combinational therapy and monotherapy groups of NA the baseline Lp(a) levels were 98,0±44,8 and 71,3±21,8 mg/dL, respectively, р<0,0001; total cholesterol (TC) 4,6±0,9 and 5,8±1,2 mM/L, р<0,0001 and low density lipoproteides cholesterol (LDL-C) 2,7±0,8 and 3,6±1,2 mM/L, р<0,05. Patients from the statins monotherapy and NA groups had significant differences by TC (4,6±1,1 and 5,8±1,2, р<0,05) and LDL-C (2,6±0,9 and 3,6±1,2, р<0,0001). In NA responders, the decrease of Lp(a) was 38%, p<0,05, in combination therapy group, and 32%, p<0,01, in monotherapy by NA group. In statin monotherapy group the Lp(a) level did not decrease. The differences were found, in the parameters of lipid profile and lipoproteides (LP) subfractions depending on the type of treatment used. In the general group of combination therapy there was significant decrease of TC, TG, LDL-C and very low density lipoproteides, and there was decline of the levels of antiatherogenic subfractions of high density lipoproteides (HDL). In monotherapy by NA group there was significant decrease of atherogenic small LDL (sLDL) from 6,9±6,7 to 3,9±4,1 mg/dL, р=0,012, and there was increase of antiatherogenic HDL subfractions. In patients on monotherapy by statins, the LP subfractions profile did not differ significantly. Conclusion. The decrease of Lp(a), atherogenic sLDL and potentially atherogenic small HDL, increase of antiathrogenic LP subfractions makes it to conclude on complex positive influence of NA on the lipoproteid subfractional profile in patients with increased Lp(a) levels, not taking statins

Nicotinic acid supplementation in diet favored intramuscular fat deposition and lipid metabolism in finishing steers.

Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH, participates in many biochemical processes, e.g. lipid metabolism. The main purpose of this study was to investigate the effects of dietary NA on carcass traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred finishing steers. Sixteen steers with the similar body weight and at the age of 24 months were randomly allocated into control group (feeding basal diet) and NA group (feeding basal diet + 1000 mg/kg NA). All experimental cattle were fed a 90% concentrate diet and 10% forage straw in a 120-day feeding experiment. The results showed that supplemental NA in diet increased longissimus area, intramuscular fat content (17.14% vs. 9.03%), marbling score (8.08 vs. 4.30), redness (a*), and chroma (C*) values of LD muscle, but reduced carcass fat content (not including imtramuscular fat), pH24 h and moisture content of LD muscle, along with no effect on backfat thickness. Besides, NA supplementation increased serum HDL-C concentration, but decreased the serum levels of LDL-C, triglyceride, non-esterified fatty acid, total cholesterol, and glycated serum protein. In addition, NA supplementation increased G6PDH and ICDH activities of LD muscle. These results suggested that NA supplementation in diet improves the carcass characteristics and beef quality, and regulates the compositions of serum metabolites. Based on the above results, NA should be used as the feed additive in cattle industry.

Nicotinic Acid

Nicotinic acid is back in the spotlight of controversy, and it therefore appears appropriate to consider its benefits and possible problems. Jackevicius et al have just published their concerns that per capita use of nicotinic acid in the United States far exceeds that in Canada, almost 6-fold by their calculation, with Niaspan as the main prescription product in both the countries. Apparently, their economic comparison and implied excess use in the United States were stimulated by 2 recent studies considered to cause uncertainty regarding nicotinic acid, the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/ High Triglycerides: Impact on Global Health Outcomes (AIMHIGH) trial and the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2THRIVE) study. The AIM-HIGH trial reported that in patients with atherosclerotic cardiovascular (CV) disease already treated for a low-density lipoprotein cholesterol (LDL-C) level of 71 mg/dL (1.84 mmol/L), no incremental benefit occurred with the addition of nicotinic acid to statin therapy over 36 months, although significant improvements resulted in high-density lipoprotein cholesterol (HDL-C) and triglycerides. In HPS2THRIVE, nicotinic acid, combined with the antiflushing agent laropiprant, did not decrease CV risk further in the presence of statin therapy, and there was a question of increased risk of nonfatal but serious side effects. In the case of HPS2-THRIVE, the starting overall LDL-C was 1.64 mmol/L (63 mg/dL). Both of these studies involved patients on a statin with proven CV disease and essentially at the target for the high-CV risk patient of LDL-C <70 mg/dL. Showing significant benefit in this situation appears problematic, and possibly, the deck was stacked against nicotinic acid for showing more benefit due to the guideline LDL-C levels being already achieved on a statin. Nevertheless, such results must be put in context, analyzed, and debated. A National Lipid Association statement supports continued use of nicotinic acid as a statin adjunct, especially in patients with low HDL-C and high triglycerides, and points out that in the case of laropiprant in HPS2-THRIVE, the laropiprant may be a problematic factor. It is also appropriate to review that nicotinic acid has supportive evidence-based medicine, despite the current concerns. As can be summarized, there is ample evidence from multiple varied-approach studies of the benefit of a targeted reduction in LDL-C for CV disease prevention. Nicotinic acid can contribute to this LDL-C reduction in many situations. The Coronary Drug Project (CDP) was conducted between 1966 and 1975 and assessed the long-term efficacy and safety of 5 medications in men aged 30 to 64 years, with electrocardiogram-documented previous myocardial infarction (MI). At the end of the trial, nicotinic acid showed a modest benefit in decreasing definite nonfatal recurrent MI, but total mortality was not decreased. Nicotinic acid was discontinued at the end of the CDP. However, with a mean follow-up of 15 years, almost 9 years after the end of the CDP trial (the patients were not taking nicotinic acid during these 9 years after the CDP), the mortality in the nicotinic acid group was 11% lower than in the placebo group (52.0% vs 58.2%; P 1⁄4 .0004). In the Cholesterol Lowering Atherosclerosis Study using colestipol plus nicotinic acid, it was demonstrated by quantitative coronary angiography that coronary artery plaque regression is achievable with statistical significance. In a meta-analysis involving 11 clinical trials of nicotinic acid, including 9959 patients with nicotinic acid either used alone or combined with other lipid-lowering therapy, Lavigne and Karas calculated the odds ratio (OR) for CV disease events. Nicotinic acid use was associated with a significant decrease in combined end points of any CV disease event (OR: 0.66; 95% confidence interval [CI]: 0.49-0.89; P 1⁄4 .007) and major coronary heart disease (CHD) events (OR: 0.75; 95% CI: 0.59-0.96; P 1⁄4 .02). Nicotinic acid did not significantly alter the incidence of stroke, and the difference in HDL-C between treatment arms did not have a significant association with the extent of nicotinic acid effect on outcomes. In a combined analysis of 4 major studies that evaluated the effect of nicotinic acid on glucose levels, on coronary artery stenosis progression utilizing quantitative coronary angiography, and on various clinical events in a combined total of 407 patients, Phan et al found that nicotinic acid over 3 years was associated with increased blood glucose levels and an increased risk of an impaired fasting glucose but not actual diabetes mellitus.

Comparison of efficacy of the phosphate binders nicotinic acid and sevelamer hydrochloride in hemodialysis patients

Hyperphosphatemia is a significant risk factor for the development of ectopic calcification and coronary artery diseases in patients on hemodialysis (HD), and must be controlled with the use of phosphate binders. Studies comparing the effects of sevelamer and nicotinic acid, both similar non-calcium and non-aluminum phosphate binders, are not available. In this study, 40 patients on HD with a serum phosphorus level of more than 6 mg/dL were enrolled. After a two week washout period without phosphate binders, the patients were randomly divided into two equal groups (n = 20) and were started on nicotinic acid or sevelamer for a period of four weeks. The dose of nicotinic acid used was 500 mg and that of sevelamer was 1600 mg daily. Blood samples were drawn for the measurement of the total calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (Chol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid and parathyroid hormone (PTH). Patients receiving sevelamer showed a significant reduction in serum P level (2.2 ± 0.69 mg/dL; P <0.0001) in comparison with the nicotinic acid group (1.7 ± 1.06 mg/dL; P = 0.004). Reduction in the Ca-P product was significantly different in the two groups; in the sevelamer group, it was 21 ± 7; (P <0.0001) while in the nicotinic acid group, it was 16 ± 11 (P = 0.007). Also, patients on sevelamer showed greater reduction in the mean TG level (38.9 ± 92 mg/dL; P = 0.005). No significant changes were observed in the mean serum Ca, total Chol, HDL, LDL, ALP and iPTH levels in the two study groups. Our short-term study suggests that although nicotinic acid reduced hyperphosphatemia, sevelamer showed higher efficacy in controlling hyperphosphatemia as well as the Ca-P product.

Abstract 2219: High Dose Modified-release Nicotinic Acid Reduces Carotid Atherosclerosis: a Randomized, Placebo-controlled Magnetic Resonance Study

Background: Large clinical outcome studies (AIM-HIGH and HPS-2THRIVE) are underway testing the strategy of adding high dose nicotinic acid (NA) to statin treatment. However, the effect of this on atherosclerosis progression is unknown. Hypothesis: Nicotinic acid 2g daily would reduce change in carotid wall area, assessed by MRI, compared to placebo. Methods: We performed a double-blind randomized placebo-controlled study of 2g once daily modified release NA added to background statin therapy in 71 patients with low HDL-C &lt;40 mg/dL and either known coronary heart disease with type 2 diabetes mellitus or carotid / peripheral atherosclerosis The pre-specified primary end point was the change in carotid artery wall area, assessed by MRI, after 1 year. We compared the treatment effect using a mixed effect model adjusting for baseline covariates. Results: 22/35 NA and 29/36 placebo patients completed MRI at all time points. Baseline characteristics were similar. In the NA treated group, HDL-C increased 23% (39±6 to 48±7 mg/dL), and LDL-C decreased 19% (85±23 to 69±21 mg/dL). At 12 months, the NA group had a significantly higher reduction in carotid wall area compared to placebo (adjusted treatment difference [95% CI] = −1.64 mm 2 [−3.12, −0.16]; P=0.03). Median (IQR) change in carotid wall area was −1.42 mm 2 (−2.65, 0.79) for NA and 0.47 mm 2 (−0.97, 2.59) for placebo. At 12 months the change in carotid plaque index (calculated by the recognised method of normalising wall area to total vessel area) was also reduced compared to placebo (treatment difference −0.016 [−0.03, −0.0022]; P = 0.02). Even as early as six months, although there was no treatment difference for change in absolute carotid wall area (−0.98 mm 2 [−2.45, 0.49]; P = 0.2), change in carotid plaque index was already significantly lower in the NA treated group (−0.016 [−0.03, 0.0019]; P = 0.03). Conclusions: This is the first demonstration that addition of high dose modified-release nicotinic acid, to statin-treated patients with low HDL-C, reduces carotid atherosclerosis at 12 months compared to placebo.

Role of the nicotinic acid group in NAADP receptor selectivity

Nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown to be an intracellular Ca 2+-releasing messenger in a wide variety of systems to date. Its actions are both potent and highly specific despite differing structurally from the endogenous cellular co-factor and its precursor, NADP, only in the substitution of a hydroxyl for the amine group at the 3′ position of the pyridine ring. This substitution allows NAADP to bind to a membrane-localized binding site in sea urchin egg homogenates with an IC 50 at least 1000-fold greater than that of NADP as measured by competition radioligand binding assays. This suggests that the NAADP receptor protein must include certain features in the NAADP binding site that regulate this specificity. In order to investigate this interaction, we synthesised a series of NAADP analogues differing from NAADP at the 3′ position of the pyridine ring that included both simple carboxylic acid analogues as well as a series of chemical isosters. We then investigated both their affinity for the NAADP binding site in sea urchin egg homogenates and their ability to activate the NAADP sensitive Ca 2+ channel. We hereby show that a negative charge at the 3′ position is an important determinant of affinity but the protein displays a large tolerance for the size of the group. Furthermore, the protein does not easily accommodate multiple charged groups or large uncharged groups.

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound: mechanism of action.

The cardioprotective effects of an antilipolytic compound, nicotinic acid, on arrested-reperfused myocardium were investigated in the isolated in situ pig heart preparation. Hearts were preperfused for 15 min in the presence of (5-3H)-glucose and (U-14C)-palmitic acid. Half of the hearts were then perfused with 0.08 mM nicotinic acid for an additional 15-min period, while the remaining control hearts received unmodified perfusion. Arrest was then induced in all animals for 2 h using hypothermic K+ cardioplegia, followed by 60 min of normothermic reperfusion. In control hearts, there were significantly greater levels of long-chain acyl Co-A and acyl carnitine and lower levels of membrane phospholipids than in the nicotinic acid group. While nicotinic acid inhibited beta-oxidation during pre-ischemia and reperfusion, it also prevented the degradation of membrane phospholipids. The net result was a reduction of free fatty acid accumulation during arrest and reperfusion in the nicotinic acid group. Glycolysis, as reflected in 3H2O production, was significantly increased by nicotinic acid administration. In the control heart as compared to the nicotinic acid group, the incorporation of 14C-label from palmitate into triglyceride and cholesterol during arrest was enhanced, while incorporation into phospholipids was depressed. The cardioprotective effects of nicotinic acid were demonstrated by decreased release of creatine kinase and improved coronary blood flow, and cardiac contractility in the reperfused myocardium supplemented with nicotinic acid compared to the control group. These results suggest that nicotinic acid significantly protects the arrested-reperfused myocardium by a) preventing elevation of myocardial fatty acid levels, b) stimulating glycolysis by limiting fatty acid oxidation, c) inhibiting degradation of membrane phospholipids, and d) preventing accumulation of fatty acid metabolites with harmful detergent properties.

Influence of Nicotinic, Picolinic and Pyridine-3-sulfonic Acids on Cholesterol Metabolism in the Rat

The addition of 1% of nicotinic, picolinic or pyridine-3-sulfonic acid to a cholesterol-free rat diet for 3 weeks did not affect serum cholesterol levels. Liver cholesterol levels of the nicotinic acid-fed rats were lower than those of the controls. When these compounds were fed at 1% of the diet to rats also receiving 2% cholesterol and 0.5% cholic acid, all test groups displayed elevated serum cholesterol levels and the nicotinic acid group also had a higher liver cholesterol content than did the controls. Hepatic cholesterogenesis from sodium acetate-1-C14 in rats fed 1% nicotinic acid or pyridine-3-sulfonic acid was significantly reduced, whereas that of the group fed picolinic acid was below that of the control group but not significantly so.