Long-term endometrial and breast safety of a specific, standardized soy extract.

OBJECTIVE: To assess the effects of an oral soy isoflavone extract (Phytosoya) on endometrium and breast in postmenopausal women treated for 3 years. METHODS: A total of 395 postmenopausal women were included in this international prospective, open-label study. The number of patients who completed the 3-year study was 197. The women were treated for 3 years with a specific, standardized soy isoflavone extract (total 70 mg/day). Endometrial biopsy, transvaginal ultrasonography and mammography were performed before and after 3 years of treatment. RESULTS: No case of hyperplasia/cancer was diagnosed among the 192 interpretable biopsies at 3 years. Only one case of simple hyperplasia was diagnosed among 197 post-baseline interpretable biopsies. The endometrial safety of this extract has been demonstrated (point estimate 0.5%). There was no statistically significant change in endometrial thickness after 3 years (98.4% inactive or atrophic and 0.3% proliferative endometrium at 1 year). Mammography results showed no notable change from baseline. No patient in any set developed an ACR classification of 4 or 5 after 3 years of treatment. The global safety was rated as either 'excellent' or 'good' by 99.1% of investigators and 99.0% of patients after 3 years of treatment. The adverse events were as follows: eight patients had metrorrhagia and seven patients had at least one breast adverse event: three patients had 'breast pain', two patients reported 'breast tenderness' and two patients had 'hypertrophic breast' (most of them were possibly treatment-related). CONCLUSIONS: As no case of hyperplasia was diagnosed among the 301 interpretable biopsies at 1 year and there was only one case of simple hyperplasia in the 197 post-baseline biopsies at 3 years, the endometrial safety of this extract has been demonstrated. Furthermore, as demonstrated by the lack of change in endometrial thickness associated with the histologic results, we suggest that this extract does not exert a mitogenic effect on the endometrium. These results suggest that daily administration of 70 mg of a specific, standardized isoflavone extract for 3 years could be a safe treatment for both endometrium and breast.

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.

Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity.

The green tea extract AR25 is an 80% ethanolic dry extract standardized at 25% catechins expressed as epigallocatechin gallate (EGCG). In vitro, green tea extract AR25 exerts a direct inhibition of gastric and pancreatic lipases and a stimulation of thermogenesis. In an open study, the effects of extract AR25 were evaluated in moderately obese patients. After 3 months, body weight was decreased by 4.6% and waist circumference by 4.48%. These results suggest the green tea extract AR25 to be a natural product for the treatment of obesity, which exerts its activity by several ways: inhibition of lipases and stimulation of thermogenesis.

Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity.

The thermogenic effect of tea is generally attributed to its caffeine content. We report here that a green tea extract stimulates brown adipose tissue thermogenesis to an extent which is much greater than can be attributed to its caffeine content per se, and that its thermogenic properties could reside primarily in an interaction between its high content in catechin-polyphenols and caffeine with sympathetically released noradrenaline (NA). Since catechin-polyphenols are known to be capable of inhibiting catechol-O-methyl-transferase (the enzyme that degrades NA), and caffeine to inhibit trancellular phosphodiesterases (enzymes that break down NA-induced cAMP), it is proposed that the green tea extract, via its catechin-polyphenols and caffeine, is effective in stimulating thermogenesis by relieving inhibition at different control points along the NA-cAMP axis. Such a synergistic interaction between catechin-polyphenols and caffeine to augment and prolong sympathetic stimulation of thermogenesis could be of value in assisting the management of obesity. International Journal of Obesity (2000) 24, 252-258

Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein.

OBJECTIVE: To evaluate the efficacy and safety of Harpagophytum in the treatment of hip and knee osteoarthritis comparatively with the slow-acting drug for osteoarthritis, diacerhein. PATIENTS AND METHODS: A multicenter, randomized, double-blind, parallel-group study was conducted in 122 patients with hip and/or knee osteoarthritis. Treatment duration was four months and the primary evaluation criterion was the pain score on a visual analog scale. Harpagophytum 2,610 mg per day was compared with diacerhein 100 mg per day. RESULTS: After four months, considerable improvements in osteoarthritis symptoms were seen in both groups, with no significant differences for pain, functional disability, or the Lequesne score. However, use of analgesic (acetaminophen-caffeine) and nonsteroidal anti-inflammatory (diclofenac) medications was significantly reduced in the Harpagophytum group, which also had a significantly lower rate of adverse events. CONCLUSION: In this study, Harpagophytum was at least as effective as a reference drug (diacerhein) in the treatment of knee or hip osteoarthritis and reduced the need for analgesic and nonsteroidal anti-inflammatory therapy.

Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis.

In a double-blind, randomized, multicentre clinical study, the efficacy and tolerance of a herbal medicine product, Harpadol (6 capsules/day, each containing 435 mg of powdered cryoground powder Harpagophytum procumbens), was compared with diacerhein 100 mg/day in the treatment, for 4 months, of 122 patients suffering from osteoarthritis of the knee and hip. Assessments of pain and functional disability were made on a 10 cm horizontal visual analogue scale; severity of osteoarthritis was evaluated by Lequesne's index. Spontaneous pain showed a significant improvement during the course of the study and there was no difference in the efficacy of the two treatments. Similarly, there was a progressive and significant reduction in the Lequesne functional index and no statistical difference was found between Harpadol and diacerhein. At completion of the study, patients taking Harpadol were using significantly less NSAIDs and antalgic drugs. The frequency of adverse events was significantly lower in the Harpadol group. The most frequent event reported was diarrhea, occurring in 8.1% and 26.7% of Harpadol and diacerhein patients respectively. The global tolerance assessment by patients at the end of treatment favoured Harpadol. The results of this study demonstrate that Harpadol is comparable in efficacy and superior in safety to diacerhein.

Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans.

BACKGROUND: Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system. OBJECTIVE: We investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans. DESIGN: Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch, and dinner. RESULTS: Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen. Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P < 0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines. CONCLUSIONS: Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.

Influence of human obesity on the metabolic fate of dietary long- and medium-chain triacylglycerols.

The metabolic fate of an oral long-chain-triacylglycerol (LCT) load and of a mixed oral LCT and medium-chain-triacylglycerol (MCT) load was followed for 6 h in eight control and eight obese subjects with normal postabsorptive triacylglycerol concentrations. Labeled triacylglycerol and indirect calorimetry were used. Results showed that LCTs were less oxidized in obese than in control subjects (3.2+/-0.5 compared with 6.0+/-0.4 g, P < 0.01). Moreover, the amount of LCT oxidized was negatively correlated with fat mass (r = -0.77, P < 0.01). Appearance in plasma of dietary triacyglycerol-derived long-chain fatty acids was blunted in obese subjects and it was negatively related to fat mass (r = -0.84, P < 0.01) and positively to LCT oxidation (r = 0.70, P < 0.01). On the contrary, MCT oxidation was not altered in obese subjects compared with control subjects. Furthermore, the proportion of MCTs oxidized was higher in both groups compared with LCTs (x+/-SEM: 57.5+/-2.6% compared with 15.2+/-1.6%, P < 0.01, n = 16). Our conclusion is that obesity is associated with a defect in the oxidation of dietary LCTs probably related to an excessive uptake by the adipose tissue of meal-derived long-chain fatty acids. MCTs, the oxidation of which is not altered in obesity, could therefore be of interest in the dietary treatment of obesity.

Efficacy and safety of Buxus sempervirens L. preparations (SPV(30)) in HIV-infected asymptomatic patients: a multicentre, randomized, double-blind, placebo-controlled trial.

The objective of the present study was to compare the efficacy and safety of two doses of SPV(30) in HIV asymptomatic patients. The study was designed as a randomized double-blind multicentre trial of two doses of SPV(30) (990 mg/d and 1980 mg/d) versus placebo. 145 previously untreated subjects with asymptomatic HIV infection (CDC group IV) and CD4 cell counts between 250 and 500 × 10(6)/1 were recruited. There was a statistically significant difference in therapeutic failures between groups in favor of SPV(30) 990 mg including decreases of CD4 cell count < 200 × 10(6)/1 and/or number of clinical aggravations (progression to AIDS or AIDS related complex). The treatment groups differed statistically in the rate of disease progression also in favor of SPV(30) 990 mg/d. Fewer patients receiving SPV(30) 990 mg/d had at the end an increase of viral load greater than 0.5 log (P = 0.029). No severe side-effects were reported in the 3 groups. From these results we conclude that SPV(30) 990 mg/d has beneficial effects in HIV asymptomatic patients and appears to delay the progression of HIV disease.