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      An Extract of Pomegranate Fruit and Galangal Rhizome Increases the Numbers of Motile Sperm: A Prospective, Randomised, Controlled, Double-Blinded Trial

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          Pomegranate fruit ( Punica granatum) and galangal ( Alpinia galanga) have separately been shown to stimulate spermatogenesis and to increase sperm counts and motility in rodents. Within traditional medicine, pomegranate fruit has long been used to increase fertility, however studies on the effect on spermatogenesis in humans have never been published. With this study we investigated whether oral intake of tablets containing standardised amounts of extract of pomegranate fruit and powder of greater galangal rhizome (Punalpin) would increase the total number of motile spermatozoa. The study was designed as a prospective, randomized, controlled, double-blinded trial. Enrolment was based on the mean total number of motile spermatozoa of two ejaculates. The participants delivered an ejaculate after 4–8 days of tablet intake and two ejaculates just before they stopped taking the tablets. Seventy adult men with a semen quality not meeting the standards for commercial application at Nordic Cryobank, but without azoospermia, were included in the study. Participants were randomized to take tablets containing extract of pomegranate fruit (standardised with respect to punicalagin A+B, punicalin and ellagic acid) and freeze-dried rhizome of greater galangal (standardised with respect to 1′S-1′-acetoxychavicol acetate) or placebo on a daily basis for three months. Sixty-six participants completed the intervention (active treatment: n = 34; placebo: n = 32). After the intervention the total number of motile spermatozoa was increased in participants treated with plant extracts compared with the placebo group (p = 0.026). After three months of active treatment, the average total number of motile sperm increased by 62% (from 23.4 to 37.8 millions), while for the placebo group, the number of motile sperm increased by 20%. Sperm morphology was not affected by the treatment. Our findings may help subfertile men to gain an improved amount of motile ejaculated sperm by taking tablets containing preparations of pomegranate fruit extract and rhizome of greater galangal.

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          Most cited references 35

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          Dietary phenolics: chemistry, bioavailability and effects on health.

          There is much epidemiological evidence that diets rich in fruit and vegetables can reduce the incidence of non-communicable diseases such as cardiovascular diseases, diabetes, cancer and stroke. These protective effects are attributed, in part, to phenolic secondary metabolites. This review summarizes the chemistry, biosynthesis and occurrence of the compounds involved, namely the C6-C3-C6 flavonoids-anthocyanins, dihydrochalcones, flavan-3-ols, flavanones, flavones, flavonols and isoflavones. It also includes tannins, phenolic acids, hydroxycinnamates and stilbenes and the transformation of plant phenols associated with food processing (for example, production of black tea, roasted coffee and matured wines), these latter often being the major dietary sources. Events that occur following ingestion are discussed, in particular, the deglycosylation, glucuronidation, sulfation and methylation steps that occur at various points during passage through the wall of the small intestine into the circulatory system and subsequent transport to the liver in the portal vein.We also summarise the fate of compounds that are not absorbed in the small intestine, but which pass into the large intestine where they are degraded by the colonic microflora to phenolic acids, which can be absorbed into the circulatory system and subjected to phase II metabolism prior to excretion. Initially, the protective effect of dietary phenolics was thought to be due to their antioxidant properties which resulted in a lowering of the levels of free radicals within the body.However, there is now emerging evidence that themetabolites of dietary phenolics,which appear in the circulatory systemin nmol/L to low mmol/L concentrations, exertmodulatory effects in cells through selective actions on different components of the intracellular signalling cascades vital for cellular functions such as growth, proliferation and apoptosis. In addition, the intracellular concentrations required to affect cell signalling pathways are considerably lower than those required to impact on antioxidant capacity. The mechanisms underlying these processes are discussed.
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            Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing.

            The antioxidant activity of pomegranate juices was evaluated by four different methods (ABTS, DPPH, DMPD, and FRAP) and compared to those of red wine and a green tea infusion. Commercial pomegranate juices showed an antioxidant activity (18-20 TEAC) three times higher than those of red wine and green tea (6-8 TEAC). The activity was higher in commercial juices extracted from whole pomegranates than in experimental juices obtained from the arils only (12-14 TEAC). HPLC-DAD and HPLC-MS analyses of the juices revealed that commercial juices contained the pomegranate tannin punicalagin (1500-1900 mg/L) while only traces of this compound were detected in the experimental juice obtained from arils in the laboratory. This shows that pomegranate industrial processing extracts some of the hydrolyzable tannins present in the fruit rind. This could account for the higher antioxidant activity of commercial juices compared to the experimental ones. In addition, anthocyanins, ellagic acid derivatives, and hydrolyzable tannins were detected and quantified in the pomegranate juices.
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              Oxidative stress and male infertility--a clinical perspective.

              Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                2 October 2014
                8 October 2014
                : 9
                : 10
                [1 ]Laboratory of Reproductive Biology, Scientific Unit, Regional Hospital of Horsens, Horsens, Denmark
                [2 ]Nerthus ApS, Lejre, Denmark
                [3 ]Department of Chemical Engineering, Biotechnology and Environmental Technology, Faculty of Engineering, University of Southern Denmark, Odense, Denmark
                [4 ]Department of Public Health, Section for Biostatistics, University of Aarhus, Aarhus, Denmark
                [5 ]Centre of Andrology, Fertility Clinic, Department D, Odense University Hospital, Odense, Denmark
                University of Kansas Medical Center, United States of America
                Author notes

                Competing Interests: Two of the authors (IG and HBJ) are commercializing the product; however, their company, Nerthus APS, has not contributed financially to the study. The full names of the two filed patent applications are: Dry preparation of Alpinia galanga or Alpinia conchigera with high content of 1′S-1′-acetoxychavicol acetate:(Application no. PCT/EP2014/061880); and Composition for enhancing semen quality in a male subject: (Application no. PCT/EP2014/061851). The product name of the food supplement: Punalpin®. There are no further patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Conceived and designed the experiments: IG HBJ JF. Performed the experiments: JF MDKF LPC. Analyzed the data: ETP IG HBJ LPC JF MDKF. Contributed reagents/materials/analysis tools: IG HBJ. Wrote the paper: JF MDKF IG HBJ LPC ETP.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 9
                The study was funded by Centre for Science and Research of Alternative Treatment (VIFAB), who played no other role in the study. Grant number 1002282. VIFAB does not exist anymore. Nerthus ApS is owned by authors Ina Giversen (IG) and Henrik Byrial Jakobsen (HBJ). Nerthus ApS did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section.
                Research Article
                Medicine and Health Sciences
                Complementary and Alternative Medicine
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                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.



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