Evaluation of the chondroprotective action of N-acetylglucosamine in a rat experimental osteoarthritis model.

It has been demonstrated that oral administration of N-acetylglucosamine (GlcNAc) alleviates the symptoms of osteoarthritis (OA). The aim of the present study was to elucidate the molecular mechanisms for the chondroprotective action of GlcNAc in OA. Biomarkers for type II collagen degradation and synthesis were evaluated, as were histopathological changes, using a rat anterior cruciate ligament transection (ACLT)-induced OA model. Changes in the expression of genes in the cartilage were assessed via DNA microarray and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results indicated that ACLT induced histopathological changes of articular cartilage, whereas oral administration of GlcNAc (1,000 mg/kg/day for 28 days) significantly suppressed these changes. Additionally, GlcNAc significantly decreased levels of a type II collagen degradation marker in sera compared with that in the ACLT group, although there were no significant changes in the levels of a type II collagen synthesis marker. Furthermore, DNA microarray and reverse transcription-quantitative polymerase chain reaction results demonstrated that GlcNAc treatment downregulated the expression of periostin, which is likely involved in the degradation of cartilage, whereas GlcNAc upregulated the expression of lipocalin 2, which is involved in the regulation of chondrocyte proliferation and differentiation. In conclusion, the results of the present study suggest that GlcNAc is able to suppress the histopathological changes induced by OA and exhibits a chondroprotective action by inhibiting type II collagen degradation in the articular cartilage, possibly via modulation of the expression of inflammatory and chondroprotective molecules, including periostin and lipocalin 2.

Effect of N-acetylglucosamine administration on cartilage metabolism and safety in healthy subjects without symptoms of arthritis: A case report.

N-acetylglucosamine (GlcNAc) is a widely accepted treatment for osteoarthritis (OA); however, its effect on healthy individuals is poorly understood. To evaluate the effect of GlcNAc administration on healthy subjects that do not exhibit symptoms of arthritis, the present randomized, double-blind, placebo-controlled study was performed. In the present study, 68 male and female Japanese participants, without symptomatic and radiographic evidence of OA, were enrolled and randomly allocated to receive placebo or GlcNAc (500 or 1,000 mg/day) for 16 weeks. Effects were evaluated using biomarkers for type II collagen degradation and synthesis, collagen type II cleavage (C2C), procollagen type II carboxy-terminal propeptide (PIICP) and their ratio (C2C/PIICP). Furthermore, safety assessments were performed via physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that there was no significant change in the biomarkers for type II collagen degeneration and synthesis during and after the intervention with the placebo and two GlcNAc groups. However, subgroup analysis using subjects with impaired cartilage metabolism (who exhibited enhanced type II collagen degradation and reduced type II collagen synthesis) indicated that the C2C levels were significantly decreased at 8 (P<0.05) and 16 (P<0.01) weeks during the intervention in the two GlcNAc (500 mg and 1,000 mg/day) groups, compared with the placebo group. In contrast, PIICP levels were not notably different in the placebo and two GlcNAc groups. The C2C/PIICP ratio was markedly decreased at 12 and 16 weeks during the intervention in the two GlcNAc groups, compared with the placebo group. Moreover, no supplement-related adverse events were observed during and after the intervention. In conclusion, these observations indicate that oral administration of GlcNAc at doses of 500 and 1,000 mg/day improves cartilage metabolism in healthy subjects without apparent adverse effects.

Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial.

Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, -0.23 and -0.34 mg/dl, respectively) compared to the placebo group (-0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (-0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects.

Dose-dependent changes in the levels of free and peptide forms of hydroxyproline in human plasma after collagen hydrolysate ingestion.

The presence of hydroxyproline (Hyp)-containing peptides in human blood after collagen hydrolysate ingestion is believed to exert beneficial effects on human health. To estimate the effective beneficial dose of these peptides, we examined the relationship between ingested dose and food-derived Hyp levels in human plasma. Healthy volunteers (n=4) ingested 30.8, 153.8 and 384.6 mg per kg body weight of collagen hydrolysate. The average plasma concentration of Hyp-containing peptides was dose-dependent, reaching maximum levels of 6.43, 20.17 and 32.84 nmol/ml following ingestion of 30.8, 153.8 and 384.6-mg doses of collagen hydrolysate, respectively. Ingesting over 153.8 mg of collagen hydrolysate significantly increased the average concentrations of the free and peptide forms of Hyp in plasma. The Hyp absorption limit was not reached with ingestion of as much as 384.6 mg of collagen hydrolysate. These finding suggest that ingestion of less than 30.8 mg of collagen hydrolysate is not effective for health benefits.

Effect of anserine ingestion on hyperglycemia and the autonomic nerves in rats and humans.

Anserine and L-carnosine are similar dipeptides synthesized by muscles of vertebrates. The functional role of anserine is unknown, although previous studies showed hypoglycemic effects of carnosine through autonomic nerves. Thus, we evaluated the effects of anserine on blood glucose levels and the neural activities. Intraperitoneal administration of specific doses of anserine to hyperglycemic rats reduced hyperglycemia and plasma glucagon concentrations, whereas thioperamide eliminated the effects of anserine. Intraduodenal injection of 0.1 mg anserine to anesthetized rats after laparotomy suppressed sympathetic nerve activity and enhanced activity of the vagal gastric efferent. In addition, oral administration of anserine reduced blood glucose levels during oral glucose tolerance testing in humans. These results suggest the possibility that anserine might be a control factor for the blood glucose, and that histaminergic nerves may be involved in the hypoglycemic effects of anserine.

Effect of anserine ingestion on the hyperglycemia and autonomic nerves in rats and humans.

Anserine and L-carnosine are similar dipeptides synthesized by muscles of vertebrates. The functional role of anserine is unknown, although previous studies showed hypoglycemic effects of carnosine through autonomic nerves. Thus, we evaluated the effects of anserine on blood glucose levels and neural activities. Intraperitoneal administration of specific doses of anserine to hyperglycemic rats reduced hyperglycemia and plasma glucagon concentrations, whereas thioperamide eliminated the effects of anserine. Intraduodenal injection of 0.1 mg anserine to anesthetized rats after laparotomy suppressed sympathetic nerve activity and enhanced activity of the vagal gastric efferent. In addition, oral administration of anserine reduced blood glucose levels during oral glucose tolerance testing in humans. These results suggest the possibility that anserine might be a control factor for blood glucose, and that histaminergic nerves may be involved in the hypoglycemic effects of anserine.

Intestinal absorption and blood clearance of L-histidine-related compounds after ingestion of anserine in humans and comparison to anserine-containing diets.

Anserine is a bioactive dipeptide found in muscles and brains of vertebrates, but little is known about the kinetics of its absorption into blood and the clearance after the ingestion of anserine or anserine-containing diets. This study investigated time-dependent changes in the concentrations of l-histidine-related compounds from deproteinized blood. The concentration of anserine peaked and then decreased to zero, whereas the concentration of pi-methylhistidine gradually increased, at which point anserine was not detected. Thus, ingested anserine is absorbed intact in human blood and is hydrolyzed to pi-methylhistidine and beta-alanine by serum and tissue carnosinases. Moreover, the crossover study suggests that there was no significant difference in absorption under curves of anserine between anserine alone and anserine-containing diet, whereas there was significant difference in the peak concentration of anserine. This is the first study to demonstrate intestinal absorption and blood clearance of anserine.