sodium-benzoate and hippuric-acid

Sodium benzoate is widely used in the Alimentary Industry at low doses for its antimicrobial action. It has also been used as a liver function test. The principle is to evaluate the liver capacity for conjugation of glycine to benzoic acid and to form hippuric acid which is excreted in the urine. In hyperammonemic syndromes, secondary to enzymatic deficiency of the urea cicle, sodium benzoate has the property to act as an alternative way of nitrogen excretion to urinary hippurate instead of urea. Recently, it has been proposed as a therapeutic alternative in cirrhotic patients with portal systemic encephalopathy. Historical, biochemical and clinical data which constitute the principles to validate its clinical application in Hepatology are reviewed in this manuscript.

Topics: Acetates; Adult; Animals; Child; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glycine; Hepatic Encephalopathy; Hippurates; Humans; Hyperammonemia; Liver Cirrhosis; Liver Function Tests; Male; Metabolism, Inborn Errors; Mice; Molecular Structure; Rats; Sodium Benzoate; Urea

The objective of this study was to evaluate the comparative effects of benzoic acid and sodium benzoate in feeds on digesta pH, urinary pH, and growth performance for nursery pigs. A total of 432 pigs (6.9 ± 0.9 kg BW) were assigned to eight treatments (6 pigs per pen, replication = 9) in a randomized complete block design with initial body weight (BW) as a block and fed for 41 d in three phases (7/17/17 d, respectively). Treatments were 1) a basal diet (NC), 2) NC + 0.25% bacitracin methylene disalicylate (antibiotic; bacitracin: 250 g/t feed; PC), 3) NC + 0.25% benzoic acid, 4) NC + 0.35% benzoic acid, 5) NC + 0.50% benzoic acid, 6) NC + 0.30% sodium benzoate, 7) NC + 0.40% sodium benzoate, and 8) NC + 0.60% sodium benzoate. Growth performance and fecal scores were measured for each phase. One gilt representing the median BW of each pen was euthanized to collect digesta from the stomach, proximal jejunum, distal jejunum, and cecum, and urine. The PC tended to improve average daily gain (ADG) in phase 1 (P = 0.052) and phase 2 (P = 0.093) as well as average daily feed intake (ADFI) in phase 2 (P = 0.052). Overall, increasing supplemental benzoic acid tended to have a quadratic effect on ADG (P = 0.094), but no difference in ADFI was observed. Increasing supplemental sodium benzoate showed a quadratic effect (P < 0.05) on ADG and linearly increased (P < 0.05) ADFI. Urinary pH linearly decreased (P < 0.05) with increasing supplemental benzoic acid, but was not affected by supplemental sodium benzoate. Increasing supplemental benzoic acid or sodium benzoate linearly increased (P < 0.05) benzoic acid content in digesta of the stomach. Increasing supplemental benzoic acid or sodium benzoate also linearly increased (P < 0.05) urinary hippuric acid. However, the PC did not decrease urinary pH or increase urinary benzoic acid and hippuric acid. With slope-ratio assay using ADG and urinary hippuric acid as dependent variables and benzoic acid intake as an independent variable, the relative bioavailability of benzoic acid compared to sodium benzoate was not different. In conclusion, supplementation of benzoic acid and sodium benzoate could improve the growth performance of nursery pigs. The relative bioavailability of sodium benzoate to benzoic acid of nursery pigs did not differ based on BW gain and urinary hippuric acid.. Newly weaned pigs are exposed to various challenges during the postweaning period, resulting in retarded growth performance. Dietary antibiotics have been used to reduce the negative impacts of weaning stress. However, use of antibiotics in feeds has been phased out in response to concerns associated with microbial resistance. In this study, dietary benzoic acid was supplemented to promote growth performance and increase urinary hippuric acid of nursery pigs. The sodium benzoate may show similar effects with benzoic acid on growth performance and urinary hippuric acid, as sodium benzoate can be highly converted to benzoic acid via the action of gastric acid in stomach. Thus, this study aimed to investigate the effects of increasing benzoic acid and sodium benzoate supplementation on growth performance and acidification of digesta and urine, and to investigate the comparative effects of benzoic acid and sodium benzoate supplemented in diets for nursery pigs. Dietary benzoic acid and sodium benzoate improved body weight gain and increased urinary hippuric acid of nursery pigs. Both sodium benzoate and benzoic acid had similar effects when fed to nursery pigs for their body weight gain and metabolism. Benzoic acid, however, had a stronger effect acidifying urine compared with sodium benzoate.

Topics: Animal Feed; Animals; Bacitracin; Benzoic Acid; Diet; Female; Hydrogen-Ion Concentration; Sodium; Sodium Benzoate; Sus scrofa; Swine

Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure.

Topics: Adolescent; Adult; Anticonvulsants; Blood Glucose; Cross-Over Studies; Diet; Female; Food Preservatives; Glucagon; Glucose; Glycine; Hippurates; Homeostasis; Humans; Insulin; Male; Metabolome; ortho-Aminobenzoates; Overweight; Sodium Benzoate; Young Adult

The objective of this study was to compare the effects of sodium-benzoate (NaB) with those of benzoic acid (BAc) on growth performance of piglets as well as nutrient digestibility, nitrogen and mineral balance, urinary pH, and the urinary excretion of BAc and hippuric acid (HAc). The study was conducted with 120 weaning piglets (6.5 kg body weight), divided in four groups (15 replicates of two piglets each), which received (1) a basal diet (Control), or the basal diet supplemented with (2) 4 g NaB per kg (Group 4NaB), (3) 3.5 g BAc per kg (Group 3.5BAc) or (4) 5 g BAc per kg (Group 5BAc). Performance data were monitored over a 42-day period. Urine and faeces were collected from day 28-33 in metabolic cages with five piglets per treatment. Piglets of Groups 3.5BAc and 5BAc had similarly a considerably improved average daily gain and feed intake (p < 0.05). Performance of Group 4NaB was not significantly different from the other groups. Compared to the Control, the nitrogen retention was only improved in Group 5BAc (p < 0.05); the other groups showed intermediate values. In the supplemented groups, most of the BAc was excreted as HAc in urine, but only Groups 3.5BAc and 5BAc had reduced urinary pH (p < 0.05). Daily intake and faecal and urinary excretion of P and Ca were not affected by the treatment. The molar excess of Na in Group 4NaB was reflected by higher renal excretion of Na compared to the other groups (p < 0.05).

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Benzoic Acid; Diet; Dietary Supplements; Feces; Female; Hippurates; Male; Minerals; Nitrogen; Sodium Benzoate; Swine

Certain urinary metabolites are the product of gut microbial or mammalian metabolism; others, such as hippurate, are mammalian-microbial 'co-metabolites'. It has previously been observed that Crohn's disease (CD) patients excrete significantly less hippurate than controls. There are two stages in the biosynthesis of this metabolite: 1) gut microbial metabolism of dietary aromatic compounds to benzoate, and 2) subsequent hepatorenal conjugation of benzoate with glycine, forming hippurate. Differences in such urinary co-metabolites may therefore reflect systemic consequences of altered gut microbial metabolism, though altered host metabolic pathways may also be involved.. It was hypothesised that reduced hippurate excretion in CD patients was due to alterations in the gut microbiota, and not differences in dietary benzoate, nor defective host enzymatic conjugation of benzoate. 5 mg/kg sodium benzoate were administered orally to 16 CD patients and 16 healthy controls on a low-benzoate diet. Baseline and peak urinary hippurate excretion were measured.. Baseline hippurate levels were significantly lower in the CD patients (p = 0.0009). After benzoate ingestion, peak urinary levels of hippurate did not differ significantly between the cohorts. Consequently the relative increase in excretion was significantly greater in CD (p = 0.0007).. Lower urinary hippurate levels in CD are not due to differences in dietary benzoate. A defect in the enzymatic conjugation of benzoate in CD has been excluded, strongly implicating altered gut microbial metabolism as the cause of decreased hippurate levels in CD.

Topics: Administration, Oral; Adult; Aged; Bacteria; Crohn Disease; Female; Follow-Up Studies; Gastrointestinal Tract; Hippurates; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Prognosis; Sodium Benzoate; Young Adult

Inborn errors of urea synthesis result in hyperammonemia. Sodium benzoate (SB) therapy has been beneficial in the treatment of hyperammonemia. It conjugates with glycine to form hippurate, which is then excreted. SB has also been used to treat children with nonketotic hyperglycinemia (NKH), where glycine is removed, on conjugation, as hippurate. In mammalian liver mitochondria, SB is activated by an ATP-dependent reaction to its CoA ester, before conjugation with glycine. Pantothenic acid (PA) is the precursor of CoA. In this investigation, increasing the amounts of PA increased CoA levels in HepG2 cells. It also significantly increased formation of hippurate in SB-treated cells. These findings suggest a beneficial effect of PA on the SB therapy in children with NKH as well as hyperammonemia.

Topics: Cell Line; Hippurates; Humans; Metabolism, Inborn Errors; Pantothenic Acid; Sodium Benzoate

Topics: Benzoates; Biomedical Research; Glucuronates; Hepatitis; Hepatitis A; Hepatolenticular Degeneration; Hippurates; Jaundice; Jaundice, Obstructive; Liver Cirrhosis; Liver Function Tests; Pharmacology; Sodium; Sodium Benzoate; Urine

Topics: Benzoates; Body Fluids; Glycine; Hippurates; Humans; Sodium Benzoate; Urinary Tract

Topics: Benzoates; Hippurates; Humans; Injections; Liver Diseases; Liver Function Tests; Sodium Benzoate

Topics: Benzoates; Hippurates; Humans; Sodium Benzoate; Urine

Topics: Benzoic Acid; Eating; Glucuronates; Hippurates; Humans; Liver; Liver Function Tests; Sodium Benzoate

Topics: Hepatitis; Hepatitis A; Hippurates; Humans; Liver Diseases; Liver Function Tests; Sodium; Sodium Benzoate