Letter to the editor UC-II® Undenatured type II collagen: update to analytical methods.

Supplementation with UC-II® undenatured type II collagen has been shown to provide joint health benefits for both healthy adults and adults with knee osteoarthritis in controlled clinical trials. These trials used UC-II® materials with undenatured type II collagen characterized by an ELISA method that utilizes a monoclonal antibody specific for epitopes expressed by undenatured type II collagen protein only. In 2014, we modified the sample preparation part of the ELISA method in order to reduce the amount of time devoted to this procedure. We undertook these modifications in order to provide commercial manufacturers with a streamlined assay methodology better aligned with their product testing requirements. In doing so, it altered the percent of undenatured collagen now reported for UC-II® undenatured type II collagen. The intent of this letter is to clarify that the UC-II® materials used in the published clinical research cited herein, and the commercially available ingredient, remain identical and to describe the rationale for the change in the extraction method.

l-Carnitine Supplementation in Recovery after Exercise.

Given its pivotal role in fatty acid oxidation and energy metabolism, l-carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l-carnitine on the recovery process after exercise. It is demonstrated that l-carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness. The supplementation-based increase in serum and muscle l-carnitine contents is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function thereby reducing hypoxia-induced cellular and biochemical disruptions. Studies in older adults further showed that l-carnitine intake can lead to increased muscle mass accompanied by a decrease in body weight and reduced physical and mental fatigue. Based on current animal studies, a role of l-carnitine in the prevention of age-associated muscle protein degradation and regulation of mitochondrial homeostasis is suggested.

Impact of chromium dinicocysteinate supplementation on inflammation, oxidative stress, and insulin resistance in type 2 diabetic subjects: an exploratory analysis of a randomized, double-blind, placebo-controlled study.

BACKGROUND: Chromium dinicocysteinate (CDNC) is a unique chromium complex consisting of chromium, niacin, and L-cysteine. Previous preclinical and clinical studies support the safety and efficacy of CDNC in modulating oxidative stress, vascular inflammation, and glycemia in type 2 diabetes. OBJECTIVE: Herein, we report the results of several exploratory analyses conducted on type 2 diabetic subjects who previously participated in a 3-month randomized, double-blind, placebo-controlled trial and were treated with only metformin as standard diabetic care in addition to receiving the test supplementations. DESIGN: Results from 43 metformin users, who were randomly assigned to receive either placebo (P, n=13), chromium picolinate (CP, 400 µg elemental Cr(3+)/day, n=12), or CDNC (400 µg elemental Cr(3+)/day, n=18), were analyzed for blood markers of vascular inflammation, insulin resistance, and oxidative stress at baseline and at 3 months of supplementation. RESULTS: A statistically significant decrease in insulin resistance in the CDNC-supplemented cohort compared to placebo (p=0.01) was observed at 3 months. The CDNC group also demonstrated a significant reduction in insulin levels (p=0.03), protein carbonyl (p=0.02), and in TNF-α (p=0.03) compared to the placebo group. The CP group only showed a significant reduction in protein carbonyl levels (p=0.03) versus placebo. CONCLUSIONS: When controlling for diabetes medication, CDNC supplementation showed beneficial effects on blood markers of vascular inflammation, insulin resistance, and oxidative stress compared to placebo. The findings suggest that CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes.

Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.

BACKGROUND: Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC). METHODS: One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method. RESULTS: At day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups. CONCLUSION: UC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement's actions are warranted. TRIAL REGISTRATION: CTRI/2013/05/003663 ; CTRI/2013/02/003348 .

Safety and toxicological evaluation of Meratrim®: an herbal formulation for weight management.

Meratrim is a unique dietary ingredient consisting of extracts from Sphaeranthus indicus flower heads and Garcinia mangostana fruit rind. Clinical studies have demonstrated that Meratrim is effective and well-tolerated in weight management. Herein we assessed the broad spectrum safety of Meratrim in a battery of in vitro and animal toxicological studies including a sub-chronic repeated-dose 13-week oral toxicity study to determine the no-observable-adverse-effect-level (NOAEL). The LD50 levels of Meratrim in Sprague-Dawley (SD) rats, as determined by the acute oral and dermal toxicity studies, were >5000 and >2000 mg/kg body weight, respectively. The primary skin and eye irritation tests classified Meratrim as non-irritating to the skin and mildly irritating to the eye. Genotoxicity studies showed that Meratrim is non-mutagenic. In the repeated-dose 13-week oral toxicity study, SD rats were orally gavaged with Meratrim at 0, 250, 500 or 1000 mg/kg/day. No morbidity, mortality, or significant adverse events were observed either during the course of the study or on the 13th week. The NOAEL of Meratrim was concluded to be 1000 mg/kg of body weight/day in male and female SD rats. These results, combined with the tolerability of Meratrim in the human clinical trials, demonstrate the broad spectrum safety of Meratrim.

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

BACKGROUND: UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. METHODS: This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. RESULTS: After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. CONCLUSIONS: Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities.