Efficacy of a dietary supplement in dogs with osteoarthritis: A randomized placebo-controlled, double-blind clinical trial.

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA.

Effects of Protein-Rich Nutritional Composition Supplementation on Sarcopenia Indices and Physical Activity during Resistance Exercise Training in Older Women with Knee Osteoarthritis.

Older adults with knee osteoarthritis (KOA) are at high risk of sarcopenia. Protein-rich nutritional composition supplementation (PS) combined with resistance exercise training (RET) improves muscle gains and facilitates physical activity in older adults. However, whether PS augments the effects of RET on muscle mass and PA in patients with KOA remains unclear. Therefore, this study identified the effects of PS on sarcopenic indices and PA in older women with KOA subjected to an RET program. Eligible older women aged 60-85 years and diagnosed as having KOA were randomly assigned to either the experimental group (EG) or the control group (CG). Both groups performed RET twice a week for 12 weeks. The EG received additional PS during this period. Outcome measures included appendicular lean mass index, walking speed, physical activity, and scores on the Western Ontario and McMaster Universities Osteoarthritis Index-WOMAC). All measures were tested at baseline and after intervention. With participant characteristics and baseline scores as covariates, analysis of variance was performed to identify between-group differences in changes in all outcome measures after intervention. Statistical significance was defined as p < 0.05. Compared with the CG, the EG achieved greater changes in appendicular lean mass index (adjusted mean difference (aMD) = 0.19 kg/m2, p < 0.01), physical activity (aMD = 30.0 MET-hour/week, p < 0.001), walking speed (aMD = 0.09 m/s, p < 0.05), and WOMAC global function (aMD = -8.21, p < 0.001) after intervention. In conclusion, PS exerted augmentative effects on sarcopenic indices, physical activity, and perceived global WOMAC score in older women with KOA through 12 weeks of RET.

A Mixture Containing Fermented Achyranthes japonica Nakai Ameliorates Osteoarthritis in Knee Joints of Monoiodoacetate-Injected Rats.

We demonstrated the effect of a mixture containing fermented Achyranthes japonica Nakai (FS) in the context of a monosodium iodoacetate (MIA)-induced osteoarthritis animal model. The mineralization, anabolic and catabolic factors, and the amount of cytokines within the articular cartilage of rats were measured after administration of MIA. We found that dietary supplementation with methylsulfonylmethane (positive control) and FS (FS 100 mg/kg body weight [b.w.] and FS 300 mg/kg b.w.) effectively suppressed pathological changes in the knee joint and inhibited changes in the architectural and mineralization parameters. In addition, prostaglandin E2 (PGE2) and proinflammatory cytokines in the serum and catabolic factors, including matrix metalloproteinase (MMP)-3 and MMP-7 in articular cartilage, were decreased by dietary supplementation with FS in MIA-induced osteoarthritis. Based on these findings, we suggest that FS can be used for the development of potential therapies for osteoarthritis.

The influence of probiotic diet and chondroitin sulfate administration on Ptgs2, Tgfb1 and Col2a1 expression in rat knee cartilage during monoiodoacetate-induced osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common worldwide disease induced by a wide range of biochemical processes, mainly inflammation and degradation of collagen. The aim of this study, was to describe the effect of a multistrain probiotic (PB) and chondroitin sulfate (CS), administered separately or in combination, on the expression of Ptgs2, Tgfb1 and Col2a1 during monoiodoacetate-induced OA in male rats. METHODS: OA was induced in male rats by injecting monoiodoacetate in right hind knee. Therapeutic groups received 3 mg/kg of CS for 28 days and/or 1.4 g/kg of multistrain PB for 14 days. Knee cartilage were taken 30 days after monoiodoacetate injection. RNA was extracted and the expression of Ptgs2, Tgfb1 and Col2a1 were analyzed using SYBR Green 1-step real-time quantitative polymerase chain reaction. RESULTS: Induction of OA caused an upregulation in Ptgs2, Tgfb1 expression, and downregulation of Col2a1. Separate administration of PB and CS reduced Ptgs2 and Tgfb1 expressions. Their combined administration significantly decreased the expression of these pro-inflammatory cytokines, comparable to controls. Expression of Col2a1 showed similar behavior, with upregulation in therapeutic group with separate administration and the cumulative effects in case of co-administration. CONCLUSIONS: The multistrain PB diet may offer a perspective to improve the standard treatment of OA and, necessitates further investigation with clinical trials.

Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1ß-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.

PURPOSE: MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1ß (IL-1ß)-induced expression of miRNAs in human chondrocytes. METHODS: Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1ß. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors. RESULTS: Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1ß-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the 'seed-matched-sequence' for hsa-miR-140-3p. IL-1ß-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1ß-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p. CONCLUSIONS: This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.

Dietary and Supplemental Vitamin C and D on Symptom Severity and Physical Function in Knee Osteoarthritis.

Vitamins C and D have been associated with decreasing pain and increasing function but these associations are not definitive. This cross-sectional study explores what relationships supplemental and dietary intake of vitamins C and D have on pain severity and physical function in patients with knee osteoarthritis. Using data from the Osteoarthritis Initiative, we performed regression analyses to examine relationships between vitamins C and D, pain, and function. Dietary vitamin D and dietary vitamin C were divided into >90th, 50th-90th, and <50th percentile. The high percentile group for supplemental vitamin D was divided into >85th percentile, whereas the high percentile group for supplemental vitamin C was divided into >90th percentile. We found the 90th/85th percentile levels of dietary and supplemental vitamin D to be positively associated with pain (ß = 0.180; p = 0.028) and inversely related to physical function (ß = -0.150, p = 0.028), respectively. Daily intake of vitamin C showed no statistical significance. We found that supplementary vitamin D was strongly associated with lessened disability for knee OA patients. The unexpected finding that associated dietary vitamin D with greater knee pain merits further study.

Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis.

OBJECTIVE: To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. METHOD: Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D3 (n = 209) or placebo (n = 204) for 24 months. Knee effusion-synovitis volume in suprapatellar and other regions was measured on magnetic resonance imaging (MRI) using OsiriX software. The intra-class correlation coefficients (ICCs) were used to test inter- and intra-rater reliabilities. The least significant change criterion was used to define the increase/decrease in effusion-synovitis volume. RESULT: The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). CONCLUSION: This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.

A double-blind, placebo-controlled, randomised, clinical study on the effectiveness of collagen peptide on osteoarthritis.

BACKGROUND: Recent studies show that enzymatically hydrolysed collagen, the collagen peptide, is absorbed and distributed to joint tissues and has analgesic and anti-inflammatory properties. A double-blind, placebo-controlled, randomised trial with collagen peptides isolated from pork skin (PCP) and bovine bone (BCP) sources was carried out to study the effectiveness of orally supplemented collagen peptide to control the progression of osteoarthritis in patients diagnosed with knee osteoarthritis. Improvement in treatment was assessed with reduction in Western Ontario McMaster Universities (WOMAC), visual analogue scale (VAS) and quality of life (QOL) scores from baseline to 13 weeks (Visit 7). Safety and tolerability were also evaluated. RESULTS: There was significant reduction from baseline to Visit 7 in the primary end points of WOMAC and VAS scores and in the secondary end point of QOL score in subjects with PCP and BCP groups, while in subjects with placebo group the end point indices remained unaltered. Furthermore, all the score levels of WOMAC, VAS and QOL decreased significantly (P < 0.01) in the study group compared to placebo group in Visit 7. CONCLUSION: The study demonstrated that collagen peptides are potential therapeutic agents as nutritional supplements for the management of osteoarthritis and maintenance of joint health.

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.

Histomorphometric alteration of knee articular cartilage and serum alkaline phosphatase in young female mice by chronic supplementation with soybean.

The purpose of the present study was to examine the effect of soybean supplementation on cartilage thickness in the knee joint and serum levels of alkaline phosphatase (ALP) in mice. Forty female mice were fed for 6 months on one of four regimens: low protein, complete protein without soybean, and complete protein containing either 20% or 40% soybean. Body weight differences, histological and histomorphometric analysis, and ALP levels were determined and compared after 6 months. The results showed a significant increase in serum ALP activity and cartilage thickness in both groups fed on soybean-containing diets, compared with the other groups. Additionally, the number of chondrocytes was significantly increased (p < 0.001) in the group taking the 40% soybean regimen, and the proteoglycan content of the intracellular fluid in the tibia was higher in those groups taking soybean. In conclusion, the present study suggests that soybean supplementation is capable of stimulating ALP production and reducing cartilage loss in young female mice. Soybean supplementation during childhood may therefore be potentially useful in protecting joints.

[Uncontrolled clinical study of the efficacy of ambulant fasting in patients with osteoarthritis]. / Unkontrollierte klinische Studie zur Wirksamkeit ambulanten Heilfastens bei Patienten mit Arthrose.

OBJECTIVE: To study the efficacy of fasting therapy according to Buchinger on pain, state of health, and articular function in patients with osteoarthritis. PATIENTS AND METHODS: Uncontrolled pilot study in which 30 patients (22 women, 8 men) with osteoarthritis (Kellgren stages I-III) of the hand (N = 10), hip (N = 8) and knee (N = 12) underwent ambulant fasting therapy according to Buchinger for 2 weeks with 3 pre-fast days, 8 fast days (300 kcal) and 4 re-feed days as well as follow-up 4 and 12 weeks afterwards. ASSESSMENT CRITERIA: Global intensity of pain (visual analogue scale, VAS); joint pain with activity, with start of walking, at rest (VAS); pressure pain threshold; articular function; health-related quality of life (SF-36 including Physical Component Score and Mental Component Score); Western Ontario and McMasters Universities Arthrose Index (WOMAC); painDETECT-questionnaire (Pfizer); analgesics; weight; body mass index (BMI); waist circumference; blood pressure; pulse and a variety of serological parameters. RESULTS: Pain, state of health, and articular function improved significantly; significant reduction in weight, BMI, and waist circumference during fasting and over the complete course of the study; analgesics could be reduced. No abnormalities in autonomous, metabolic, or blood parameters were observed. CONCLUSION: Medically supervised fasting can have a positive impact on the symptoms of patients with moderate osteoarthritis. This finding must be consolidated by controlled studies that include higher numbers of patients.

[The influence of the vitamin-mineral complex upon the blood vitamin, calcium and phosphorus of patients with ostreoarthrosis].

In research in which 11 osteoarthrosis patients with osteoarthrosis of the knee-joint of II-III degree and 18 healthy people took part, it has been shown that sufficiency with vitamin C, carotinoids and calcium of osteoarthrosis patients was worse than that of healthy people. These micronutrients blood plasma level in both groups was less than the lower border of normal sufficiency. Whereas patients from both groups were adequately supplied with vitamins A, E, B2 and phosphorus. Addition of vitamin-mineral complex to patients ration course 30 days resulted in eliminating insufficiently of vitamin C, carotinoids, beta-carotin, calcium and in hardly noticable changes of initial high levels of vitamin A, E, B and phosphoris. These nutrients deficit disappeared while there was no noticeable change in the initial optimal provision with vitamins B2, A and E. Thus, there is no doubt in arguments in favour of additional enrichment with vitamins and calcium of osteoarthrosis patients diet.

Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study.

OBJECTIVE: To determine whether vitamin E affects change in cartilage volume in patients with knee osteoarthritis (OA). METHODS: In a double blind, placebo controlled trial, 136 patients with knee OA (American College of Rheumatology clinical and radiographic criteria) were randomized to receive vitamin E (500 IU) or placebo for 2 years. Tibial cartilage volume was measured by magnetic resonance imaging at the beginning and end of the study. RESULTS: Baseline characteristics were similar in the 2 groups (67 vitamin E, 69 placebo); there were more women in the vitamin E group, 42 (63%) vs 33 (48%) in the placebo group. One hundred seventeen subjects (59 vitamin E, 58 placebo) completed the study. Loss of medial and lateral tibial cartilage was similar in subjects treated with vitamin E and placebo (mean +/- SD: medial 157 +/- 209 vs 187 +/- 220 micro m3 placebo, p = 0.51; lateral 186 +/- 258 vs 251 +/- 216 micro m3, p = 0.19). There were no significant differences between the vitamin E and placebo treated groups in improvement of symptoms from baseline. Dietary levels of antioxidants (vitamin C, beta carotene, retinol equivalents) had no effect on cartilage volume loss. CONCLUSION: Vitamin E does not appear to have a beneficial effect in the management of knee OA: it does not affect cartilage volume loss or symptoms.

Cetylated fatty acids improve knee function in patients with osteoarthritis.

OBJECTIVE: To determine the benefit of cetylated fatty acids (CFA) on knee range of motion and function in patients with osteoarthritis (OA). METHODS: Sixty-four patients with chronic knee OA were evaluated at baseline and at 30 and 68 days after consuming either placebo (vegetable oil; n = 31) or CFA (Celadrin; n = 33). Evaluations included physician assessment, knee range of motion with goniometry, and the Lequesne Algofunctional Index (LAI). RESULTS: After 68 days, patients treated with CFA exhibited significant (p < 0.001) increase in knee flexion (10.1 degrees) compared to patients given placebo (1.1 degrees). Neither group reported improvement in knee extension. Patient responses to the LAI indicated a significant (p < 0.001) shift towards functional improvement for the CFA group (-5.4 points) after 68 days compared to a modest improvement in the placebo group (-2.1 points). CONCLUSION: Compared to placebo, CFA provides an improvement in knee range of motion and overall function in patients with OA of the knee. CFA may be an alternative to the use of nonsteroidal antiinflammatory drugs for the treatment of OA.