A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

The special formulation MA212 (Rosaxan) is composed of rosehip (Rosa canina L.) puree/juice concentrate, nettle (Urtica dioica L.) leaf extract, and devil's claw (Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (pU < 0.001; pt < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (pChi < 0.001) and patients (pChi < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients.

Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan.

Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.

Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body's defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects.

PURPOSE: The effect of brewers' yeast (1,3)-(1,6)-beta-D-glucan consumption on the number of common cold episodes in healthy subject was investigated. METHODS: In a placebo-controlled, double-blind, randomized, multicentric clinical trial, 162 healthy participants with recurring infections received 900 mg of either placebo (n = 81) or an insoluble yeast (1,3)-(1,6)-beta-D-glucan preparation (n = 81) per day over a course of 16 weeks. Subjects were instructed to document each occurring common cold episode in a diary and to rate ten predefined infection symptoms during an infections period, resulting in a symptom score. The subjects were examined by the investigator during the episode visit on the 5th day of each cold episode. RESULTS: In the per protocol population, supplementation with insoluble yeast (1,3)-(1,6)-beta-glucan reduced the number of symptomatic common cold infections by 25% as compared to placebo (p = 0.041). The mean symptom score was 15% lower in the beta-glucan as opposed to the placebo group (p = 0.125). Beta-glucan significantly reduced sleep difficulties caused by cold episode as compared to placebo (p = 0.028). Efficacy of yeast beta-glucan was rated better than the placebo both by physicians (p = 0.004) participants (p = 0.012). CONCLUSION: The present study demonstrated that yeast beta-glucan preparation increased the body's potential to defend against invading pathogens.

Cinnamon and health.

Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.

Effects of aged garlic extract on arterial elasticity in a placebo-controlled clinical trial using EndoPAT™ technology.

Cardiovascular diseases are the main cause of death in the industrialized world, with the main risk factors being elevated blood pressure and blood lipid levels, leading to arterial stiffness and arteriosclerosis. In this study, we examined the effect of aged garlic extract (AGE) on arterial elasticity, using the EndoPAT™ technology in subjects with slightly elevated blood pressure. This randomized double-blind, placebo-controlled clinical trial examined 57 subjects over a period of 12 weeks, with EndoPAT™ measurements taken at 0 and 12 weeks; in addition, changes in blood pressure were analyzed. The positive effect of AGE on blood pressure values previously reported was confirmed. The results revealed a significant decrease in blood pressure in the AGE group, and in particular diastolic blood pressure. Using the EndoPAT™ technology, the augmentation index (AI) was analyzed, which measures arterial stiffness calculated via pulse waveform analysis of the PAT signal; lower AI values reflect better arterial elasticity. The AGE group exhibited a significant improvement in arterial elasticity, measured as AI75, by 21.6%. The result of this well-controlled clinical trial confirmed the positive effect of AGE on blood pressure. To the best of our knowledge, for the first time, the effect of AGE on arterial elasticity could be proven using the EndoPAT™ methodology. These results not only demonstrate the positive effects of AGE on the relevant risk factors of cardiovascular diseases, but also the direct effect on arterial elasticity. These data clearly indicate that AGE may exert several positive direct effects on the development and progression of cardiovascular diseases.

Therapeutic effect of 1,5-pentanediol for herpes simplex labialis: a randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Most episodes of recurrent herpes labialis are self-limited and mild, but can be troublesome when they occur frequently with painful and unsightly lesions. Therefore, there has been much interest in developing agents that can suppress outbreaks in addition to being therapeutically effective. The objective of the present study was to examine the prophylactic and therapeutic efficacy of 1,5-pentanediol (PD) gel in patients with recurrent episodes of herpes labialis. METHODS: In this placebo-controlled, randomized, double-blind clinical trial, a total of 105 patients with frequent episodes of recurrent herpes were randomized to either PD or placebo. During the 26-week prophylactic phase of the study, the patients applied PD gel or placebo gel twice daily to both lips. Upon recurrence of an episode, a 5-day therapy phase started during which the gel was to be applied eight times daily. After the therapy phase, the patient resumed prophylactic treatment twice daily until the next herpes episode. The main outcome measures were number of herpes episodes during the prophylactic phase of 26 weeks, and successful therapy of occurring herpes episodes with a 5-day treatment. RESULTS: There was no significant difference in recurrence rate between the two groups (P>0.05). During recurrence there was a statistically significant improvement regarding the therapeutic effect of the symptoms "blistering," "swelling," and "pain" in the PD group. The global evaluation of efficacy by the investigators and patients showed a statistically significant superiority for PD as opposed to placebo (P<0.001). CONCLUSION: Under the conditions used in the present study, PD did not show any prophylactic effect against recurrence of herpes episodes. A significantly better therapeutic effect of PD over placebo could be demonstrated on the symptoms "blistering," "swelling," and "pain." PD was very safe as no side effects were observed during the course of the study.

Rosa canina - Rose hip pharmacological ingredients and molecular mechanics counteracting osteoarthritis - A systematic review.

BACKGROUND: The successful use of rose hip for the treatment of osteoarthritis is well documented. Several randomized placebo controlled double-blind studies, as mono or combination therapy, have demonstrated treatment efficacy as well as excellent tolerability. PURPOSE: This review focuses on the molecular mechanism underlying the clinical effects of rose hip in osteoarthritis (OA). METHODS: The database Medline was screened - using the search term "Rosa canina" or "rose hip" - for publications on pharmacological or mechanistic studies with relevance to OA; in addition for findings on pharmacologically active constituents as well as clinical studies. The screening results were complemented by following-up on cited literature. RESULTS: In particular, 24 pharmacological studies on Rosa canina or preparations thereof were considered relevant. Potent antioxidant radical scavenging effects are well documented for numerous rose hip constituents besides Vitamin C. Furthermore, anti-inflammatory activities include the reduction of pro-inflammatory cytokines and chemokines, reduction of NF-kB signaling, inhibition of pro-inflammatory enzymes, including COX1/2, 5-LOX and iNOS, reduction of C-reactive protein levels, reduction of chemotaxis and chemoluminescence of PMNs, and an inhibition of pro-inflammatory metalloproteases. CONCLUSION: The antioxidant and anti-inflammatory effects of Rosa canina match its clinical action - especially considering new findings on the pharmacological disease pattern of OA. The entirety of several compounds including phenolics, terpenoids, galactolipids, carotenoids, fruit acids and fatty oils can be considered responsible for the observed pharmacological and clinical effects. Further research is needed to eludicate how and in which manner single rose hip compounds interact with their molecular pharmacological targets.

Nutritional supplementation: is it necessary for everybody?

Mineral nutrients, vitamins, and trace elements are essential for the growth and development of a multicellular organism. Today, an adequate supply of nutrients is often unattainable solely through a well-balanced diet, so a targeted, individually designed dietary supplement regime is necessary. Nutrient deficiency, which is impossible to detect through plasma levels alone, is reliably detected through the intracellular measurement of the nutrient levels in the blood. Two case studies presented here indicate the need for supplementation as improvement in nutritional behavior could not replenish already exhausted nutrient reservoirs. Only supplementation was able to significantly boost nutrient levels and confer beneficial effects on general welfare, physical performance, and resistance to infections. Therefore, it appears that nutritional supplements are advisable for everyone, but more research is needed, especially on an intracellular level, to corroborate these findings.

Efficacy and tolerability of a Rhodiola rosea extract in adults with physical and cognitive deficiencies.

During a 12-wk drug monitoring study, the efficacy and safety of a Rhodiola rosea extract given in combination with vitamins and minerals (vigodana(R)) were tested in 120 adults (83 women and 37 men, ages 50-89 y) with physical and cognitive deficiencies. Two different dosage regimens were chosen. One group of 60 patients (group 1) took 2 capsules orally in the morning after breakfast, and the other group (group 2) took 1 capsule after breakfast and 1 after lunch. Three medical examinations were performed during the course of the study (at baseline, after 6 wk, and after 12 wk). The evaluated symptoms were divided into physical disturbances such as exhaustion, decreased motivation, daytime sleepiness, decreased libido, sleep disturbances, and cognitive complaints (eg, concentration deficiencies, forgetfulness, decreased memory, susceptibility to stress, irritability). A statistically highly significant improvement (P<.001) in physical and cognitive deficiencies was observed in the overall group, as well as in the separately evaluated groups 1 and 2. In addition, the time needed to complete a digit connection test decreased significantly in all groups (P<.001). Improvements in group 1 were more pronounced than in group 2, however, indicating that the intake of 2 capsules after breakfast is more effective than the intake of 1 capsule after breakfast and 1 after lunch. Global assessment of efficacy revealed that treatment was "very good" or "good" for 81% of patients, as reported by physicians, and for 80%, as reported by patients. Ninety-nine percent of patients and physicians rated safety as "good" or "very good." No adverse events occurred during the course of the study. The results of this drug monitoring study are very promising, but they still need to be corroborated by future placebo-controlled clinical trials.

Black cohosh and St. John's wort for climacteric complaints: a randomized trial.

OBJECTIVE: To investigate the efficacy of the fixed combination of black cohosh (Cimicifuga racemosa) and St. John's wort (Hypericum perforatum) extracts in women with climacteric complaints with a pronounced psychological component. METHODS: In this double-blind randomized placebo-control study, 301 women experiencing climacteric complaints with psychological symptoms were treated with ethanolic St. John's wort extract and isopropanolic black cohosh extract or a matched placebo for 16 weeks. Climacteric complaints were evaluated by means of the Menopause Rating Scale mean score, and psychological complaints were evaluated using the Hamilton Depression Rating Scale sum score. RESULTS: The mean (+/- standard deviation) Menopause Rating Scale score decreased 50% (0.46 +/- 0.13 to 0.23 +/- 0.13) in the treatment group and 19.6% (0.46 +/- 0.14 to 0.37 +/- 0.15) in the placebo group. The Hamilton Depression Rating Scale total score decreased 41.8% in the treatment group (18.9 +/- 2.2 to 11.0 +/- 3.8 points), and 12.7% in the placebo group (18.9 +/- 2.1 to 16.5 +/- 4.3). The treatment was significantly (P < .001) superior to placebo in both measures. There were no relevant group differences regarding adverse events, laboratory values, or tolerability. CONCLUSION: This fixed combination of black cohosh and St. John's wort is superior to placebo in alleviating climacteric complaints, including the related psychological component. LEVEL OF EVIDENCE: I.

Safety and tolerance of ester-C compared with regular ascorbic acid.

The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.

Lipid-lowering effect of 2 dosages of a soy protein supplement in hypercholesterolemia.

The lipid-lowering effect of a soy-based protein supplement was evaluated in an 8-week randomized, placebo-controlled trial in patients with hypercholesterolemia. A total of 117 patients (63 men and 54 women) received soy protein, either 15 or 25 g/d or placebo. In the active treatment groups low-density lipoprotein cholesterol levels decreased significantly by 5.9% and 1.1% respectively, but increased by 3.6% with placebo. Total serum cholesterol and apolipoprotein B levels changed significantly in a similar manner. High-density lipoprotein cholesterol, triglycerides, homocysteine, folic acid, and vitamin B12 levels did not change significantly compared with baseline in any of the study groups. All preparations were well tolerated. Soy protein 25 g/d was twice as effective as 15 g/d. In conclusion, soy protein supplementation may effectively reduce serum cholesterol levels and therefore is likely to diminish the risk for cardiovascular disease.

Effect of cod liver oil on symptoms of rheumatoid arthritis.

In this pilot study, 43 patients with rheumatoid arthritis ingested 1 g of cod liver oil (one capsule) daily for 3 months. Decreases occurred in morning stiffness (52.4%; P<10(-3)), painful (42.7%) and swollen (40%) joints (P= 10(-3) each), and pain intensity (67.5%). Ratings of "good" or "very good" were awarded by 68% of the patients for efficacy and by 95% for tolerability. Eleven patients reported nonsevere adverse effects that in 3 cases may have been related to the study preparation. Cod liver oil can be recommended for the treatment of rheumatoid arthritis.

Impulse magnetic-field therapy for erectile dysfunction: a double-blind, placebo-controlled study.

This double-blind, placebo-controlled study assessed the efficacy of 3 weeks of impulse magnetic-field therapy for erectile dysfunction (ED). Twenty volunteers who suffered from ED or orgasmic disturbances were randomly assigned to either active treatment or placebo (n = 10 each). Efficacy was assessed in terms of intensity and duration of erection, general well-being, sexual activity, and warm sensation in the genital area. In the active-treatment group, all efficacy endpoints were significantly improved at study end (P < or = .01), with 80% reporting increases in intensity and duration of erection, frequency of genital warmth, and general well-being. The remaining 20%, who experienced minor improvements, were found to have an influenza-like infection after the study that may have influenced their results. Only 30% of the placebo group noted some improvement in their sexual activity; 70% had no change. No side effects were reported.

Effect of a probiotic multivitamin compound on stress and exhaustion.

This 6-month study evaluated a probiotic multivitamin preparation in 42 adult men and women suffering from stress or exhaustion. The preparation was taken daily with breakfast. A psychological-neurologic questionnaire assessed psycho-organic, central vegetative, and somatic discomforts, and a validated list of adjectives was used to indicate the effect of therapy. At the end of the study, an overall 40.7% improvement in stress was noted, representing significant improvements of 17.4% in positive conditions and of 23.3% in negative conditions (both P<.001). In addition, decreases of 29% in the frequency of infections and of 91% in gastrointestinal discomforts, both established indicators of stress, were recorded. The preparation was well tolerated. This probiotic multivitamin is suitable for reducing stress or exhaustion, or both, as well as for improving the immune system, specifically gastrointestinal health.

Efficacy and tolerability of a combination of Lyprinol and high concentrations of EPA and DHA in inflammatory rheumatoid disorders.

This 12-week drug-monitoring study was conducted to evaluate the efficacy of Sanhelios Mussel Lyprinol Lipid Complex on 50 adult men and women with inflammatory rheumatoid arthritis. A total of 34 patients required drug therapy before and during the study. By the end of the study, 21 (62%) patients were able to reduce their dosage and 13 were able to terminate drug therapy. At the end of the treatment period, 38% were regarded symptom free, and the number of patients with severe pain decreased significantly from 60% at baseline to 25% at the completion of the trial. A significant effect was observed for each investigated parameter. The special combination of Lyprinol and omega-3 fatty acids was generally very well tolerated, with only one, nonserious adverse event (mild nausea) reported. This dietary supplement may therefore be considered an effective and well-tolerated component of treatment regimens for inflammatory rheumatoid arthritis.

Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression.

In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7 years) suffering from mild to moderate depression received one tablet of either St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen depression scale (DS), Clinical Global Impression (CGI), and patients' overall evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58% in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to the efficacy of both medications. The Hypericum extract achieved 83% of the efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians (CGI) and patients indicated considerable improvement with no between-treatment differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the fluoxetine group were due to adverse reactions. Safety evaluations demonstrated only minor changes. The Hypericum preparation tested in this study is therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants.

Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: a literature review.

Abnormal lipid levels contribute significantly to the risk of coronary heart disease, a major cardiovascular disease and a serious health problem. Various dietary and pharmacologic treatments have been devised to reduce elevated blood cholesterol levels. Soy protein, soluble fiber, and plant sterol/ester-containing margarines are promising new food-component candidates that may help to realize this goal. Of particular interest in this context is the LDL:HDL ratio, a strong predictor of cardiac events. This report is a review of more than 50 recent trials to determine how such dietary components and garlic affect the LDL:HDL ratio and other lipid parameters. Consumption of new soy products containing high, fixed levels of isoflavones, cotyledon soy fiber, and soy phospholipids (Abaco and Abalon) significantly reduced the LDL:HDL ratio by up to 27%. Soluble dietary fibers such as psyllium and beta glucan from oat bran had a variable effect on LDL-cholesterol levels in the studies analyzed. Plant sterol esters, when consumed in margarines, lowered the LDL:HDL ratio by up to 22%. On average, Abacor and Abalon reduced the LDL:HDL ratio by 20%, LDL cholesterol by 15%, total cholesterol by 10%, and triglycerides by 6%, and increased HDL cholesterol by 5%. The new soy-based supplements may therefore play a valuable role in reducing cardiovascular risk.

Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial.

In this double-blind, randomized, placebo-controlled, prospective study, the clinical efficacy and tolerability of oral Hypericum extract STW 3-VI (Laif) 900 mg once daily was compared with that of placebo. A total of 140 outpatients (94 women; 46 men) with moderate depressive disorders and a 17-item Hamilton Depression Scale (HAMD-17) score of 20 to 24 were enrolled in this study. Following a single-blind placebo run-in period of 7 days, the patients were randomized to Hypericum extract 900 mg or placebo for the 6-week treatment period. Nineteen patients have been excluded from the per protocol collective because of violations of protocol regarding the scheduling of study visits and intake of study medication. The primary endpoint for treatment efficacy was the change in total HAMD-17 score at the end of the 6-week treatment period. The HAMD-17 total score decreased significantly from baseline by approximately 11.1 +/- 4.5 points (from 22.8 +/- 1.1 to 11.8 +/- 4.4) in the Hypericum group and by approximately 3.4 +/- 3.9 points (from 22.6 +/- 1.2 to 19.2 +/- 3.8) in the placebo group (P < .001). Comparable group differences in favor of Hypericum were revealed by an additional responder analysis, the von Zerssen's Adjective Mood Scale, the Clinical Global Impressions scale, and a global efficacy assessment. Tolerability was very good in both groups; neither serious adverse events nor clinically relevant changes in safety parameters were observed, and only 2 cases demonstrated a possible connection between an adverse event and the study medication. The final safety assessment showed no differences between the Hypericum extract and placebo groups. The study provided evidence that Hypericum extract STW 3-VI in a once-daily dosing regimen may be an effective and well-tolerated option for patients with moderate depressive disorders.

Botanical health products, positioning and requirements for effective and safe use.

Within the group of botanical products there is a large range of variation with regard to their properties. Some products are identical to foods while others come close to or are medicines. Botanical products are regulated differently within the different member states of the European Union (EU) and globally. They are regulated either as food or as medicinal products, and in the latter case often with simplified registration procedures. These differences are caused by differences in traditional use, in cultural and historical background, in scientific substantiation and in enforcement of current legislation. One may expect that in the future differences will remain, unless EU legislation is enacted with sufficient room for different approaches. The strengths and weaknesses of the different regulatory procedures have been reviewed and evaluated as well as the current methods for quality, efficacy and safety evaluation. Criteria to categorize botanical products have been defined, such that botanical products can be regulated under the current food and medicinal regulations. Furthermore, a decision tree has been developed as a tool to distinguish herbal medicinal products from botanical health products and vice versa, and to provide a stepwise framework for the assessment of safety and efficacy.