Tamarindus indica Seed Extract-Based Botanical Compositions Alleviate Knee Pain and Improve Joint Function in Mild-to-Moderate Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Study.

OBJECTIVE: Knee pain and reduced joint function affect the quality of life of subjects suffering from knee osteoarthritis (KOA). The present randomized, double-blind, placebo-controlled study aimed to assess the clinical efficacy of two botanical compositions, NXT15906F6 and NXT19185, in pain relief and improvement in the musculoskeletal function of knee osteoarthritis (KOA) subjects. NXT15906F6 contains ethanol/aqueous extract of Tamarindus indica seeds and aqueous ethanol extract of Curcuma longa rhizome, and NXT19185 is a combination of NXT15906F6 and an aqueous ethanol extract of Garcinia mangostana fruit rind. METHODS: The present trial recruited ninety subjects with mild-to-moderate KOA, using a radiographic Kellgren-Lawrence (KL) grading system. The participants were randomized into one of three groups (n = 30) to receive either placebo, NXT15906F6 (250 mg/day), or NXT19185 (300 mg/day) for 56 days. The change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was the primary efficacy measure of the study. Improvements in the functional scores, serum proinflammatory modulators, and cartilage degradation product in the urine samples were the secondary efficacy measures. Twenty-seven subjects in each group completed the trial. RESULTS: After the trial, NXT15906F6 and NXT19185 significantly improved (P < 0.05) the WOMAC scores from baseline compared with placebo. In the subgroup analyses, the knee pain and functional scores were significantly improved in the KL-II and KL-III grade KOA subjects. At the end of the study, the NXT15906F6- and NXT19185-supplemented participants showed significant (P < 0.05) improvement in the functional scores, inflammatory status, and collagen breakdown product in the urine samples. Summary. The present study demonstrates that NXT15906F6 and NXT19185 supplementations reduce knee pain and improve the musculoskeletal function of KOA subjects. Moreover, these herbal compositions helped reduce inflammation and inflammation-induced cartilage degeneration in the participants. NXT15906F6 and NXT19185 supplementations are further documented to be tolerable and safe to the participants.

Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects.

There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pâté (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA:arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

Krill oil attenuates left ventricular dilatation after myocardial infarction in rats.

BACKGROUND: In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. RESULTS: The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. CONCLUSIONS: Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling.

Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects.

We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.

Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers.

The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.

Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women.

Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters.

Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7.

Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K(1) is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K(1) and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K(1) and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7- to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 mug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.

Highly purified omega-3 polyunsaturated fatty acids in clinical development.

Highly purified omega-3 polyunsaturated fatty acids (PUFAs) (Omacor) is the focus of an extensive and ambitious clinical development program that seeks to build on the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione study. Studies currently in progress include very large clinical outcome trials designed to evaluate the impact of omega-3 PUFAs on death and major morbid events in defined patient populations such as individuals with heart failure or diabetes, specialist investigations in very high-risk populations such as patients requiring hemodialysis, and a range of specialized studies concerned with mechanisms of action and effects on biochemical and laboratory indices. The emergence of results from these studies can be expected to define a spectrum of indications for omega-3 PUFAs in the management of cardiovascular and renal disease.

Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans.

After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term.

Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans.

BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may reduce body fat mass (BFM) and increase lean body mass (LBM), but the long-term effect of CLA was not examined. OBJECTIVE: The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet. DESIGN: Male and female volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were included in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3 groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil). Change in BFM, as measured by dual-energy X-ray absorptiometry, was the primary outcome. Secondary outcomes included the effects of CLA on LBM, adverse events, and safety variables. RESULTS: Mean (+/- SD) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%, respectively, lower than that in the placebo group (P < 0.001). Subjects receiving CLA-FFA had 1.8 +/- 4.3% greater LBM than did subjects receiving placebo (P = 0.002). These changes were not associated with diet or exercise. LDL increased in the CLA-FFA group (P = 0.008), HDL decreased in the CLA-triacylglycerol group (P = 0.003), and lipoprotein(a) increased in both CLA groups (P < 0.001) compared with month 0. Fasting blood glucose concentrations remained unchanged in all 3 groups. Glycated hemoglobin rose in all groups from month 0 concentrations, but there was no significant difference between groups. Adverse events did not differ significantly between groups. CONCLUSION: Long-term supplementation with CLA-FFA or CLA-triacylglycerol reduces BFM in healthy overweight adults.