Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care. RESULTS: A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up. CONCLUSION: GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.

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.

Effects of intake of Lactobacillus casei subsp. casei 327 on skin conditions: a randomized, double-blind, placebo-controlled, parallel-group study in women.

Lactic acid bacteria are gut flora that play key roles in intestinal homeostasis, which may affect a variety of physiological functions. Our preliminary double-blind, placebo-controlled, parallel-group trials have suggested that intake of heat-killed Lactobacillus casei subsp. casei 327 (designated L. K-1) is effective for improving skin conditions. The aim of this study was to confirm the effect of L. K-1 intake in a randomized, double-blind, placebo-controlled, parallel-group study in healthy female volunteers. Sixty-four subjects were allocated to either the placebo food group (group P, n=32) or active food group (group A, n=32), in which subjects consumed lactobacillus K-1 50 mg (approximately 1 × 1011 bacteria) daily for 8 weeks. After excluding subjects who declined to participate (n=1), violated restrictions (n=4), or were judged ineligible by the principal investigators (n=1), data obtained with 58 subjects (30 in group A and 28 in group P) were analyzed for efficacy by comparing differences from pretrial levels between the two groups. When the level of transepidermal water loss (TEWL) was measured at the arm, the level of TEWL at week 4 of the intake period was significantly lower in group A than group P (p=0.021), suggesting an improvement of skin barrier function. Analysis of skin condition questionnaire data revealed a significant reduction in skin flakiness on the face (week 4). No adverse events were associated with intake of the test foods. The safety of L. K-1 was also confirmed in an independent open-label trial in 11 healthy subjects who consumed excessive amounts of L. K-1 250 mg (approximately 5 × 1011 bacteria). Intake of L. K-1 may therefore be beneficial to skin condition improvement.

Evaluation of the effect of salmon nasal proteoglycan on biomarkers for cartilage metabolism in individuals with knee joint discomfort: A randomized double-blind placebo-controlled clinical study.

A randomized double-blind placebo-controlled clinical trial was conducted to evaluate the chondroprotective action of salmon nasal cartilage proteoglycan on joint health. The effect of oral administration of proteoglycan (10 mg/day) on cartilage metabolism was evaluated in individuals with knee joint discomfort but without diagnosis of knee osteoarthritis. The average age of patients was 52.6±1.1 years old. The effect of proteoglycan was evaluated by analyzing markers for type II collagen degradation (C1,2C) and synthesis (PIICP), and the ratio of type II collagen degradation to synthesis. The results indicated that the change in C1,2C levels significantly differed in the proteoglycan group compared with the placebo group following 16 weeks intervention among subjects with high levels of knee pain and physical dysfunction (total score of Japan Knee Osteoarthritis Measure ≥41) and subjects with constant knee pain (both P<0.05). There was a greater increase in PIICP levels in the proteoglycan group than the placebo group following intervention, although this difference was not significant in both sets of patients. Thus, the C1,2C/PIICP ratios decreased in the proteoglycan group, whereas they slightly increased in the placebo group following the intervention. Furthermore, no test supplement-related adverse events were observed during the intervention. Therefore, oral administration of salmon nasal cartilage proteoglycan at a dose of 10 mg/day may exert a chondroprotective action in subjects with knee joint discomfort. This effect was achieved by improving cartilage metabolism (reducing type II collagen degradation and enhancing type II collagen synthesis), without causing apparent adverse effects.

Evaluation of the effect of N-acetyl-glucosamine administration on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: A randomized double-blind placebo-controlled clinical study.

The present study aimed to evaluate the effect of N-acetyl-glucosamine (GlcNAc) on the joint health of healthy individuals without arthritic symptoms. A randomized double-blind placebo-controlled clinical trial was performed to investigate the effect of oral administration of a GlcNAc-containing test supplement (low dose, 500 mg/day and high dose, 1,000 mg/day) on cartilage metabolism in healthy individuals with a mean age of 48.6±1.3 years (range, 23-64 years) by analyzing the ratio of type II collagen degradation to type II collagen synthesis using type II collagen degradation (C2C) and synthesis (PIICP) markers. The results indicated that the changes in C2C/PIICP ratios from the baseline were suppressed in the treated with low and high doses of GlcNAc, compared with the placebo group at week 16 during intervention. To further elucidate the effect of GlcNAc, subjects with impaired cartilage metabolism were evaluated. Notably, the changes in the C2C/PIICP ratios were markedly suppressed in the groups treated with low and high doses of GlcNAc at week 16. Finally, to exclude the effect of heavy body weight on joint loading, subjects weighing <70 kg with impaired cartilage metabolism were analyzed. Notably, the changes in the C2C/PIICP ratios were suppressed in the groups treated with low and high doses of GlcNAc at weeks 12 and 16. No test supplement-related adverse events were observed during or following the intervention. Together, these observations suggest that oral administration of GlcNAc at doses of 500 mg and 1,000 mg/day exhibits a chondroprotective effect on healthy individuals by reducing the C2C/PIICP ratio (relatively decreasing type II collagen degradation and increasing type II collagen synthesis) without any apparent adverse effects.

Evaluation of the effect of a chicken comb extract-containing supplement on cartilage and bone metabolism in athletes.

In a previous study, we revealed that a commercially available product of dietary supplement containing a chicken comb extract (CCE), which is rich in hyaluronan, not only relieves joint pain and other symptoms, but also potentially improves the balance of type II collagen degradation/synthesis in patients with knee osteoarthritis. Since soccer is one of the sports most likely to cause knee osteoarthritis (OA), we evaluated the effect of a CCE-containing supplement on cartilage and bone metabolism in athletes. Fourteen and 15 subjects (all midfielders) were randomly assigned to receive the test product (test group) and the dummy placebo containing only vehicle (placebo group), respectively, for 12 weeks. The daily oral intake of the CCE-containing test product clearly decreased the urinary levels of both C-terminal crosslinked telopeptides of cartilage-specific type II collagen (CTX-II) as a type II collagen degradation marker and the N-terminal telopeptides of bone-specific type I collagen (NTx) as a marker of bone resorption at 12 weeks after the initiation of the intervention. By contrast, no significant reduction was detected in the placebo group at any timepoint during the intervention. These observations indicate that the test product is effective in inhibiting, not only cartilage degradation, but also bone remodeling. Thus, the CCE-containing supplement may be useful for the management of joint health in athletes.

Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study.

In the present study, we aimed to investigate the potential effect of a glucosamine (1,200 mg/day)-based dietary supplement combined with chondroitin sulfate and three antioxidant micronutrients, namely methylsulfonylmethane, guava leaf extract, and vitamin D (test supplement) on osteoarthritis (OA) of the knee. A 16-week, randomized, double-blinded, placebo-controlled trial was conducted involving 32 subjects with symptomatic knee OA. Clinical outcomes were measured using the Japanese Knee Osteoarthritis Measure (JKOM) for symptoms and a study diary-based visual analog scale (diary VAS) for pain at baseline and at weeks 4, 8, 12 and 16 during the 16-week intervention period. Furthermore, biomarkers for cartilage type II collagen degradation (C2C) and synovitis hyaluronan (HA) were measured. As compared with the baseline, the JKOM pain subscale was significantly improved at all of the four assessment time points in the test group, but was not at any time point in the placebo group. On the other hand, all of the four symptom subscales and the aggregated total symptoms were significantly improved in the two groups at one or more time points. However, all of these clinical improvements were greater in extent in the test group than in the placebo group, and there were significant differences between groups in the magnitude of changes from baseline for one subscale 'general activities' and the aggregated total symptoms at week 8 (P<0.05). The results of efficacy assessments with the diary VAS showed that all of the three pain subscales were significantly improved only in the test group at almost all the time points. Moreover, serum levels of C2C and HA were decreased by 10 and 25%, respectively, at week 16 in the test group, albeit not statistically significant, without any detectable changes in the placebo group. In conclusion, although the results obtained in this study were not conclusive, the tested glucosamine-based combination supplement is likely to have a beneficial effect on pain and other symptoms associated with knee OA.

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

INTRODUCTION: We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. METHODS: Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA). RESULTS: sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA. CONCLUSIONS: These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Evaluation of the effects of a supplementary diet containing chicken comb extract on symptoms and cartilage metabolism in patients with knee osteoarthritis.

We aimed to investigate whether a supplementary diet containing chicken comb extract (CCE) rich in hyaluronic acid (HA) has an effect on pain and other symptoms, as well as cartilage type II collagen (CII) metabolism in patients with knee osteoarthritis (OA). A randomized double-blind placebo-controlled study was conducted in 43 subjects with knee OA (Kellgren/Lawrence grade, mainly 1-2) comprising 22 patients receiving concurrent exercise therapy (ET) and 21 without ET (referred as ET-receivers and ET-unreceivers, respectively). Subjects were randomized to a CCE-containing diet (active diet) group administered a dose of 1,800 mg/day (containing 630 mg of CCE and approximately 60 mg of HA) and a placebo group, and the intervention was continued for 16 weeks. Symptomatic efficacy was evaluated based on the Japanese Orthopaedic Association clinical trials response criteria (JOA response criteria) and Visual analog scales (VAS) before (baseline) and during the intervention. To further examine its effect on CII metabolism, the levels of two degradation biomarkers (CTX-II and C2C) and one synthesis biomarker (CPII) were measured using urine or serum samples. Nineteen subjects (10 ET-receivers and 9 ET-unreceivers) in the active diet group and 21 subjects (10 ET-receivers and 11 ET-unreceivers) in the placebo group were finally included in the study. Compared to the baseline, subscale scores of the JOA response criteria, i.e., 'pain/walking function', 'pain/step-up and -down function' and 'aggregate total symptoms' were more intensely improved in the active diet group than in the placebo group. Moreover, subgroup analyses of ET-receivers and ET-unreceivers indicated that significant improvements were restricted to ET-receivers of the active diet group. Furthermore, VAS assessment indicated that the 'pain on pressing' subscale was significantly improved in ET-receivers of the active diet group. In addition, analysis of CII biomarkers revealed that serum C2C and CPII levels, but not the urinary CTX-II level, were increased in the active diet group. Notably, both urinary CTX-II/serum CPII and serum C2C/serum CPII ratios were reduced in the active diet group (particularly ET-unreceivers), suggesting that CII synthesis was relatively increased compared to CII degradation in the active diet group. Finally, no diet-related side effects were observed. The CCE-containing diet is likely to be effective in relieving symptoms in patients with knee OA. In addition, it has the potential to improve the balance of CII degradation/synthesis in knee OA.