Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty‐seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute–Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay for mucositis development and progression in silymarin group. Prophylactic administration of conventional form of silymarin tablets could significantly reduce the severity of radiotherapy induced mucositis and delay its occurrence in patients with head and neck cancer. Copyright © 2016 John Wiley & Sons, Ltd.     

Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized,Double‐Blinded,Placebo‐Controlled Clinical Trial

Hand–foot syndrome (HFS) is a frequent dose‐limiting adverse reaction of capecitabine in patient with gastrointestinal cancers. Silymarin is a polyphenolic flavonoid extracted from the Silybum marianum that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluated silymarin efficacy in prevention of capecitabine‐induced HFS in patients with gastrointestinal cancers, as the first human study. During this pilot, randomized, double‐blinded, placebo‐controlled clinical trial, the effect of silymarin gel 1%, which is applied on the palms and soles twice daily starting at the first day of chemotherapy for 9 weeks, on HFS occurrence was assessed. Forty patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization HFS grading scale scores were recorded at baseline and every 3 weeks during these 9 weeks. The median WHO HFS scores were significantly lower in silymarin group at the end of the 9^th week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during chemotherapy, but there was a delay for HFS development and progression in silymarin group. Prophylactic administration of silymarin topical formulation could significantly reduce the severity of capecitabine‐induced HFS and delays its occurrence in patients with gastrointestinal cancer after 9 weeks of application. Copyright © 2017 John Wiley & Sons, Ltd.     

Curcuminoid Treatment for Knee Osteoarthritis: A Randomized Double‐Blind Placebo‐Controlled Trial

Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long‐term adverse events of currently available medications including non‐steroidal anti‐inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti‐inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double‐blind placebo‐control parallel‐group clinical trial was conducted among patients with mild‐to‐moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with placebo. With respect to WOMAC subscales, there were significant improvements in the pain and physical function scores (p < 0.001) but not stiffness score (p > 0.05). There was no considerable adverse effect in both groups. To conclude, curcuminoids represent an effective and safe alternative treatment for OA. Copyright © 2014 John Wiley & Sons, Ltd.     

Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Poor compliance with conventional asthma medications remains a major problem in achieving asthma control. Nigella sativa oil (NSO) is used traditionally for many inflammatory conditions such as asthma. We aimed to investigate the benefits of NSO supplementation on clinical and inflammatory parameters of asthma. NSO capsules 500 mg twice daily for 4 weeks were used as a supplementary treatment in a randomized, double‐blind, placebo‐controlled trial in asthmatics (clinicaltrials.gov: NCT02407262). The primary outcome was Asthma Control Test score. The secondary outcomes were pulmonary function test, blood eosinophils and total serum Immunoglobulin E. Between 1 June and 30 December 2015, 80 asthmatics were enrolled, with 40 patients in each treatment and placebo groups. After 4 weeks, ten patients had withdrawn from each group. Compared with placebo, NSO group showed a significant improvement in mean Asthma Control Test score 21.1 (standard deviation = 2.6) versus 19.6 (standard deviation = 3.7) (p = 0.044) and a significant reduction in blood eosinophils by ?50 (?155 to ?1) versus 15 (?60 to 87) cells/μL (p = 0.013). NSO improved forced expiratory volume in 1 second as percentage of predicted value by 4 (?1.25 to 8.75) versus 1 (?2 to 5) but non‐significant (p = 0.170). This randomized, double‐blind, placebo‐controlled trial demonstrated that NSO supplementation improves asthma control with a trend in pulmonary function improvement. This was associated with a remarkable normalization of blood eosinophlia. Future studies should follow asthmatics for longer periods in a multicentre trial. Copyright © 2017 John Wiley & Sons, Ltd.     

Lipid‐Lowering Effects of Curcumin in Patients with Metabolic Syndrome: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low‐density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The triglyceride‐lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL‐C effect in female patients, both of which result in a decrease of T‐Chol/HDL‐C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid‐lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol‐related parameters, especially in metabolic syndrome patients. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of Ginger (Zingiber officinale) on Heavy Menstrual Bleeding: A Placebo‐Controlled,Randomized Clinical Trial

Objective: A wide range of herbal plants have been reported to treat various gynecological problems of women. This study was set out to investigate the effect of ginger (Zingiber officinale) on heavy menstrual bleeding (HMB) in high school girls. Methods: Ninety‐two young women who experienced HMB and met the inclusion criteria were recruited in this study. Participants were evaluated for six consecutive menstrual cycles. During 3 assessment cycles, their HMB was confirmed by Pictorial Blood Assessment Chart. They were then randomly allocated to two study groups to receive either ginger or placebo capsules. The participants filled in the same chart during three intervention cycles. Results: The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger‐receiving group. The decrease of blood loss in ginger‐receiving group was significantly more remarkable than that of participants receiving placebo (p < 0.001). Minimum number of participants reported adverse effects. Conclusion: HMB is highly prevalent among young women. Considering the significance of appropriate and timely treatment and also the importance of prevention of unwanted consequences, ginger may be considered as an effective therapeutic option for HMB. Copyright © 2014 John Wiley & Sons, Ltd.     

Improved Lipid Profile in Hyperlipidemic Patients Taking Vaccinium arctostaphylos Fruit Hydroalcoholic Extract: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial

Dyslipidemia is a common contributory cause of cardiovascular disease. Vaccinium arctostaphylos L. (Caucasian whortleberry) fruit is rich of anthocyanins. Anthocyanins may exert cardioprotective effects by various mechanisms such as favorably modulating dyslipidemia. Therefore, in this randomized double‐blind placebo‐controlled clinical trial with hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 20–60 years, the effects of taking a standardized whortleberry fruit hydroalcoholic extract (one 350 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 40 patients and compared with the placebo group (n = 40). The extract lowered the blood levels of total cholesterol (P < 0.001), triglyceride (P = 0.002) and low‐density lipoprotein cholesterol (LDL‐C) (P = 0.002), but increased the blood high‐density lipoprotein cholesterol (HDL‐C) levels (P < 0.001) without any significant effects on the blood levels of SGOT, SGPT and creatinine (P > 0.05) compared with the placebo group at the endpoint. Whortleberry reduced total cholesterol, triglyceride and LDL‐C 27.6%, 19.2% and 26.3%, respectively, but increased HDL‐C 37.5% compared with baseline. No adverse effects were reported. Short‐term treatment with whortleberry fruit appears safe and improves lipid profile in hyperlipidemic patients. Copyright © 2013 John Wiley & Sons, Ltd.     

Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double‐Blind Placebo‐Controlled Clinical Trial

This study aimed to examine the effects of hesperidin supplement on the glycemic parameters, oxidative DNA damage, and lipid peroxidation in patients with type 2 diabetes. Sixty‐four patients were randomly allocated to receive 500 mg/day hesperidin or placebo capsules for 6 weeks. Data on glycemic parameters, total antioxidant capacity (TAC), 8‐hydroxydeoxyguanosine (8‐OHDG), and malondialdehyde (MDA) were collected at the baseline and at the end of the study. In hesperidin group, TAC increased (0.74 ± 0.16 vs. 0.82 ± 0.18), while serum froctoseamin (5.79 ± 5.86 vs. 5.01 ± 4.95; p  = 0.001), 8‐OHDG (14.32 ± 6.4 vs. 11.00 ± 7.0; p  = 0.000), and MDA (5.78 ± 1.76 vs. 4.60 ± 0.75; p  = 0.000) decreased in comparison with the baseline values. There was a significant difference in percent change of TAC (13.35 ± 19.21 vs. 3.13 ± 10.02; p  = 0.043), froctoseamin (?10.10 ± 16.84 vs. 4.27 ± 34.646), 8‐OHDG (?25.11 ± 28.23 vs. 8.69 ± 35.41; p  = 0.000), and MDA (?16.46 ± 18.04 vs. ?1.82 ± 22.63; p  = 0.007) between hesperidin and control groups following intervention in adjusted models. These results suggest that hesperidin may improve TAC and alleviate serum froctoseamin, 8‐OHDG, and MDA levels in type 2 diabetes. Copyright © 2017 John Wiley & Sons, Ltd.     

Blood Pressure Lowering Effect of Nigella sativa L. Seed Oil in Healthy Volunteers: A Randomized,Double‐Blind,Placebo‐controlled Clinical Trial

Nigella sativa L. seeds (N. sativa) have been used as a traditional remedy for a wide range of diseases including hypertension. The present study was performed to explore the effects of N. sativa oil on blood pressure (BP) in healthy volunteers. In a double‐blind, randomized study, 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were randomly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks. The systolic and diastolic BPs, body mass index and blood levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatinine and blood urea nitrogen were determined at baseline and endpoint. Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint. Other parameters did not significantly change in both groups at the endpoint. No adverse effects were reported. In conclusion, oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects. Copyright © 2013 John Wiley & Sons, Ltd.     

Evaluation of Benefit and Tolerability of IQP‐CL‐101 (Xanthofen) in the Symptomatic Improvement of Irritable Bowel Syndrome: A Double‐Blinded,Randomised, Placebo‐Controlled Clinical Trial

Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown aetiology. There is currently no known cure, and pharmacological interventions are usually targeting symptomatic relief, where natural and herbal remedies also play a role. This study aimed to evaluate the benefit and tolerability of IQP‐CL‐101 in symptomatic IBS relief. A double‐blinded, randomised, placebo‐controlled trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME‐III criteria for IBS were randomised into two groups, given either two IQP‐CL‐101 softgels or matching placebo twice daily before main meals. The primary endpoint was the difference in change of IBS Symptom Severity Score (IBS‐SSS) after an 8‐week intake of IQP‐CL‐101 compared to placebo. After 8 weeks, subjects on IQP‐CL‐101 showed a significant reduction in IBS‐SSS (113.0 ± 64.9‐point reduction) compared to subjects on placebo (38.7 ± 64.5‐point reduction) (p < 0.001). A significant improvement could be seen as early as 4 weeks. No serious adverse events were reported throughout. IQP‐CL‐101 can be considered beneficial in the improvement of IBS symptom severity, regardless of IBS type, and therefore able to improve quality of life in patients suffering from abdominal pain and discomfort. © 2017 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.     

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof‐of‐concept,Randomized, Double‐blind,Placebo‐controlled Clinical Trial

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12‐week, randomized, double‐blind, placebo‐controlled trial. Forty‐four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low‐dose RO extract (LRE; n = 14), or high‐dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75‐g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (?28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment‐B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein‐1 and oxidized low‐density lipoprotein were significantly decreased by treatment in a dose‐dependent manner (monocyte chemoattractant protein‐1: ?35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low‐density lipoprotein: ?19.7 ± 8.5, ?13.1 ± 7.2, and ?2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.     

Perioperative Bromelain Therapy after Wisdom Teeth Extraction – A Randomized,Placebo‐Controlled,Double‐Blinded,Three‐Armed,Cross‐Over Dose‐Finding Study

Reduction in postoperative edema and inflammatory reactions is the key to the posttraumatic regeneration process. Use of bromelain is well established in this indication, but there is some controversy with regard to the optimal dosing of this drug. The aim of our study was therefore to investigate the efficacy of dosage‐dependent therapy with bromelain in patients after wisdom teeth extraction by comparing the registered dosage 1000 FIP (Fédération Internationale Pharmaceutique) against higher dosages of 3000 FIP and 4500 FIP. A total of 75 patients were randomized to one of the three dosage arms, and 68 of these patients were finally analyzed in the modified intention‐to‐treat population. Patients involved underwent two surgery sessions: one study period being conducted under treatment with bromelain and the other with placebo. Postoperative swelling determined by a 3D face scanning system was defined as the primary endpoint; further efficacy parameters were maximum swelling, pain, difficulty in swallowing, and use of analgesics. A superiority of treatment with 3000 FIP and 4500 FIP versus 1000 FIP could not be demonstrated. The analysis of pooled bromelain treatments versus placebo did, however, show a clear trend in favor of bromelain for all assessments. Adverse events did not occur more frequently under bromelain therapy compared with placebo. This study thus clearly supports the clinical relevance of treatment of postoperative conditions with bromelain, and the recommended daily dose was sufficiently effective in this trial and indication. Copyright © 2016 John Wiley & Sons, Ltd.     

IQP‐GC‐101 Reduces Body Weight and Body Fat Mass: A Randomized,Double‐Blind,Placebo‐Controlled Study

IQP‐GC‐101 is a patented blend of the standardized extracts of Garcinia cambogia, Camellia sinensis, unroasted Coffea arabica, and Lagerstroemia speciosa. These individual ingredients of IQP‐GC‐101 have each shown promise in promoting weight loss; however, the efficacy of the blend has not been established. This randomized, placebo‐controlled, double‐blind, parallel group study conducted over 14 weeks (including a 2‐week run‐in phase) aimed to investigate the efficacy and safety of IQP‐GC‐101 in reducing body weight and body fat mass in overweight Caucasian adults. Subjects took three IQP‐GC‐101 or placebo tablets, twice a day, 30 min before main meals. All subjects also adhered to a 500 kcal/day energy deficit diet with 30% of energy from fat. Ninety‐one overweight and mildly obese subjects (46 in the IQP‐GC‐101 group, 45 in the placebo group) completed the study. After 12‐week intervention, IQP‐GC‐101 resulted in a mean (±SD) weight loss of 2.26 ± 2.37 kg compared with 0.56 ± 2.34 kg for placebo (p_U = 0.002). There was also significantly more reduction in body fat mass, waist circumference, and hip circumference in the IQP‐GC‐101 group. No serious adverse events were reported. The use of IQP‐GC‐101 has been shown to result in body weight and body fat reduction in the current study, with good tolerability. © 2014 InQpharm Group Sdn Bhd. Phytotherapy Research published by John Wiley & Sons, Ltd.     

Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized,Double‐Blind,Placebo‐Controlled,Crossover Study

Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double‐blind, placebo‐controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health compared with drinking alcohol alone. Copyright © 2016 John Wiley & Sons, Ltd.     

Preliminary Safety Evaluation and Biochemical Efficacy of a Carum carvi Extract: Results from a Randomized,Triple‐Blind,and Placebo‐Controlled Clinical Trial

Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple‐blind, placebo‐controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25‐item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p < 0.01) increased, and platelet distribution width was significantly decreased after the dietary CAE treatment, as compared with placebo. No negative changes were observed in the general health status of the two groups. This preliminary study suggests that the oral intake of CAE appears to be without any adverse effects at a dosage of 30 ml daily for a period of 12 weeks. Copyright © 2014 John Wiley & Sons, Ltd.     

A Randomized,Double‐blind,Placebo‐controlled Clinical Trial Examining the Effects of Green Tea Extract on Systemic Lupus Erythematosus Disease Activity and Quality of Life

Antiinflammatory and immunomodulatory benefit of green tea (Camellia sinensis) in autoimmune disease has been proven in recent studies. The objective of this study was to assess the effects of green tea on disease activity and quality of life in systemic lupus erythematosus patients. A randomized controlled trial on subjects with lupus was conducted, and 68 patients in the age range of 39.1 ± 10.3 years and body mass index of 25.7 ± 5.21 kg/m² completed the 12‐week study. Patients were randomly divided into two groups of intervention (1000 mg green tea extract, two capsules/day) and control (1000 mg of starch, two capsules/day). Main outcome measure, systemic lupus erythematosus disease activity, was assessed by the systemic lupus erythematosus disease activity index at the first and after 3 months of intervention. In addition, patient's quality of life was evaluated by short form of quality‐of‐life questionnaire at baseline and after 3 months. Green tea extract supplementation significantly reduced disease activity in lupus patients (p < 0.004); in addition, it significantly increased the vitality (p < 0.006) and general health (p < 0.01). This study showed that daily consumption of green tea extracts for 12 weeks improves the systemic lupus erythematosus disease activity as well as some aspects of quality of life. Copyright © 2017 John Wiley & Sons, Ltd.     

Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized,Double‐Blind,Placebo‐Controlled Study

The antioxidant, anti‐inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double‐blind, placebo‐controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3‐month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty‐five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma‐glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine‐glycine, oxidized cysteine (intracellular pro‐oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation‐based diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

Adjuvant Therapy with Bioavailability‐Boosted Curcuminoids Suppresses Systemic Inflammation and Improves Quality of Life in Patients with Solid Tumors: A Randomized Double‐Blind Placebo‐Controlled Trial

Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double‐blind placebo‐controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability‐boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health‐related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL‐6) and 8 (IL‐8), TNF‐α, transforming growth factor‐β (TGFβ), high‐sensitivity C‐reactive protein (hs‐CRP), calcitonin gene‐related peptide (CGRP), substance P and monocyte chemotactic protein‐1 (MCP‐1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p < 0.001). Consistently, the magnitude of reductions in TNF‐α (p < 0.001), TGFβ (p < 0.001), IL‐6 (p = 0.061), substance P (p = 0.005), hs‐CRP (p < 0.001), CGRP (p < 0.001) and MCP‐1 (p < 0.001) were all significantly greater in the curcuminoids versus placebo group. In contrast, the extent of reduction in serum IL‐8 was significantly greater with placebo versus curcuminoids (p = 0.012). Quality of life variations were associated with changes in serum TGFβ levels in both correlation and regression analyses. Adjuvant therapy with a bioavailable curcuminoid preparation can significantly improve QoL and suppress systemic inflammation in patients with solid tumors who are under treatment with standard chemotherapy protocols. Copyright © 2014 John Wiley & Sons, Ltd.     

Cardiovascular Safety of Oral p‐Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo‐Controlled Cross‐over Clinical Trial

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p‐synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p‐Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p‐synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49‐mg p‐synephrine) given to 18 healthy subjects (nine men and nine women) in a double‐blinded, placebo‐controlled cross‐over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p‐synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p‐synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p‐synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p‐Synephrine does not act as a stimulant at the dose used. Copyright © 2016 John Wiley & Sons, Ltd.