Supplementation with a soluble ß-glucan exported from Shiitake medicinal mushroom, Lentinus edodes (Berk.) singer mycelium: a crossover, placebo-controlled study in healthy elderly.

Lentinus edodes (Shiitake) is a medicinal mushroom with a long tradition of use in Asia. The major active substance in L. edodes is a (1-6,1-3)-beta-glucan (lentinan). No clinical controlled studies have yet investigated the effect of orally administered lentinan on the immune response in healthy, elderly Caucasian subjects. We evaluated the effect and the safety of a beta-glucan from L. edodes mycelium, Lentinex, in healthy, elderly subjects in a double blind, crossover, placebo-controlled trial. Forty-two subjects were randomly allocated to two groups given orally either 2.5 mg/day Lentinex or placebo for 6 weeks; then after a washout period of 4 weeks, the alternate supplementation was given for 6 weeks. The changes in the number of B-cells were significantly different between the groups. The number ofNK cells increased significantly in both groups, but there was no significant difference between the groups. Other factors of the immune response (immunoglobulins, complement proteins, cytokines) were not altered. The safety blood variables (differential cell count, liver function, kidney function, and other blood chemistry) were not influenced by Lentinex, and the number, nature, and severity of adverse events were similar to placebo. Lentinex given orally to elderly subjects was safe and induced an increase in the number of circulating B-cells.

Intravenous administration of CP-4055 (ELACYT) in patients with solid tumours. A Phase I study.

PURPOSE: Cytarabine (ara-C) has limited activity in solid tumours. CP-4055 (ELACYT) is a novel ara-C-5'-elaidic acid ester that may circumvent this limitation. CP-4055 maximum tolerated dose (MTD), pharmacokinetics and antitumor activity have been investigated in patients with solid tumours. MATERIAL AND METHODS: Thirty-four patients (19 malignant melanoma, 8 ovarian cancers and 7 NSCLC) received CP-4055 as a 30 min, or 2 hr intravenous (IV) infusion daily for 5 consecutive days every 3 or 4 weeks (D1-5 q3w or D1-5 q4w) in a dose escalation designed study with doses ranging from 30 to 240 mg/m(2)/day. RESULTS: The most frequent CTC grade 1-2 adverse events (AEs) were nausea, fatigue, vomiting, anorexia and pyrexia. Most of the grade 3-4 AEs were neutropenia. The MTD was 200 mg/m(2)/day and 240 mg/m(2)/day for D1-5 q3w and D1-5 q4w, respectively. The MTD was independent of infusion time in the 4 week schedule. CP-4055 was maintained in plasma for up to 5-10 hr at dose levels >150 mg/m(2)/day. One objective partial response (PR) with time to progression (TTP) of 22 months was reported in an advanced malignant melanoma patient. CONCLUSION: CP-4055 was well tolerated; the majority of the AEs were of CTC grade 1. The 3 week schedule was not recommended due to neutropenic nadir between days 18-26. The recommended dose was 200 mg/m(2)/day in a D1-5 q4w schedule. Efficacy data suggest that CP-4055 might be active in treatment of solid tumours.

Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese.

Long-term supplementation with conjugated linoleic acid (CLA) reduces body fat mass (BFM) and increases or maintains lean body mass (LBM). However, the regional effect of CLA was not studied. The study aimed to evaluate the effect of CLA per region and safety in healthy, overweight and obese adults. A total of 118 subjects (BMI: 28-32 kg/m2) were included in a double blind, placebo-controlled trial. Subjects were randomised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months. CLA significantly decreased BFM at month 3 (Delta=- 0 x 9 %, P=0 x 016) and at month 6 (Delta=- 3 x 4 %, P=0 x 043) compared with placebo. The reduction in fat mass was located mostly in the legs (Delta=- 0 x 8 kg, P<0 x 001), and in women (Delta=-1 x 3 kg, P=0 x 046) with BMI >30 kg/m2 (Delta=-1 x 9 kg, P=0 x 011), compared with placebo. The waist-hip ratio decreased significantly (P=0 x 043) compared with placebo. LBM increased (Delta=+0 x 5 kg, P=0 x 049) within the CLA group. Bone mineral content was not affected (P=0 x 70). All changes were independent of diet and physical exercise. Safety parameters including blood lipids, inflammatory and diabetogenic markers remained within the normal range. Adverse events did not differ between the groups. It is concluded that supplementation with CLA in healthy, overweight and obese adults decreases BFM in specific regions and is well tolerated.

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.

Clinical trial results support a preference for using CLA preparations enriched with two isomers rather than four isomers in human studies.

CLA mixtures are now commercially available. They differ from each other with respect to their content of CLA isomers and their degree of purification. As a group of natural FA, CLA have been widely assumed to be safe. However, the suspected presence of both impurities and particular isomers might induce undesirable side effects. Despite this potential health risk, only a few CLA preparations have been tested under rigorous conditions for clinical efficacy and safety. Based on the limited results available, it is possible to suggest that preparations enriched in c9,t11 and t10,c12 isomers are preferable for human consumption compared to preparations containing four isomers, in terms both of safety and efficacy.