An extract of pomegranate fruit and galangal rhizome increases the numbers of motile sperm: a prospective, randomised, controlled, double-blinded trial

Maja D K Fedder, Henrik B Jakobsen, Ina Giversen, Lars P Christensen, Erik T Parner, Jens Fedder, Maja D K Fedder, Henrik B Jakobsen, Ina Giversen, Lars P Christensen, Erik T Parner, Jens Fedder

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01357044.

Conflict of interest statement

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.

Figures

Figure 1. Flow diagram.
Figure 1. Flow diagram.
Consort diagram showing the flow of the study participants.
Figure 2. Differences in total motile sperm…
Figure 2. Differences in total motile sperm counts (TMSCs).
Plot of the differences in TMSCs from baseline to follow-up for each participant in the active treatment receiving the combination of P. granatum fruit extract and A. galanga rhizome powder and the placebo group. Follow-up – baseline (Y-axis) represents the calculated differences in TMSC between the follow-up TMSCs following 90 days of administration of either the dry preparation of A. galanga and the P. granatum extract or the placebo and the corresponding TMSCs prior to administration (baseline). Horizontal bars indicate mean.
Figure 3. ACA content in tablets.
Figure 3. ACA content in tablets.
Amount of 1′S-1′-acetoxychavicol acetate (ACA) in the A. galanga tablets within 21 months of production date.

References

    1. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE (1992) Evidence for Decreasing Quality of Semen During Past 50 Years. BMJ 305: 609–613.
    1. Swan SH, Elkin EP, Fenster L (1997) Have sperm densities declined? A reanalysis of global trend data. Environ Health Perspect 105: 1228–1232.
    1. Jørgensen N, Joensen UN, Jensen TK, Jensen MB, Almstrup K, et al. (2012) Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open 2: e000990.
    1. Türk G, Sönmez M, Aydin M, Yüce A, Gür S, et al. (2008) Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clin Nutr 27: 289–296.
    1. Mansour SW, Sangi S, Harsha S, Khaleel MA, Ibrahim AR (2013) Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract. Asian Pac J Trop Biomed 3: 563–568.
    1. Leiva P, Rubio J, Peralta F, Gonzales GF (2011) Effect of Punica granatum (pomegranate) on sperm production in male rats treated with lead acetate. Toxicol Mech Methods 21: 495–502.
    1. Qureshi S, Shah AH, Ageel AM (1992) Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med 58: 124–127.
    1. Tzulker R, Glazer I, Bar-Ilan I, Holland D, Aviram M, et al. (2007) Antioxidant activity, polyhenol content and related compounds in different fruit juices and homogenates prepared from 29 different pomegranate accessions. J Agri Food Chem 55: 9559–9570.
    1. Mayer W, Görner A, Andrä K (1977) Punicalagin und Punicalin, zwei Gerbstoffe aus den Schalen der Granatäpfel. Justus Liebigs Annalen der Chemie 11–12: 1976–1986.
    1. Gil MI, Tomas-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA (2000) Antioxidant Activity of Pomegranate Juice and Its Relationship with Phenolic Composition and Processing. J Agric Food Chem 48: 4581–4589.
    1. Kubota K, Ueda Y, Yasuda M, Masuda A (2001) Occurrence and antioxidative activity of 1'-acetoxychavicol acetate and its related compounds in the rhizomes of Alpinia galanga during cooking. Food Flavors and Chemistry - Advances of the New Millennium 274: 601–607.
    1. Satish R, Dhananjayan R (2003) Evaluation of anti-inflammatory potential of rhizome of Alpinia galanga Linn. Biomedicine 23: 91–96.
    1. Islam MW, Zakaria MNM, Radhakrishnan R, Liu XM, Ismail A, et al. (2000) Galangal (Alpinia galanga Willed.) and Black seeds (Nigella sativa Linn.) and sexual stimulation in male mice. J Pharm Pharmacol 52 Suppl.: 278–278.
    1. Ayala C, Steinberger E, Smith DP (1996) The Influence of Semen Analysis Parameters on the Fertility Potential of Infertile Couples. J Androl 17: 718–725..
    1. World Health Organization (2010) Laboratory manual for the examination and processing of human semen, 5th edition 2010. Cambridge University Press, Cambridge, UK.
    1. Zhang Y, Wang D, Lee RP, Henning SM, Heber D (2009) Absence of Pomegranate Ellagitannins in the Majority of Commercial Pomegranate Extracts: Implications for Standardization and Quality Control. J Agric Food Chem 57: 7395–7400.
    1. Ruxton GD (2006) The unequal variance t-test is an underused alternative to Student's t-test and the Mann–Whitney U test. Behav Ecol 17: 688–690.
    1. James C, Bithell J (2000) “Bootstrap Confidence Intervals: When, Which, What? A Practical Guide for Medical Statisticians.”. Stat Med 19: 1141–1164.
    1. Bonde JP, Ernst E, Jensen TK, Hjollund NH, Kolstad H, et al. (1998) Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352: 1172–1177.
    1. Turner TT (1995) On the Epididymis and its Role in the Development of the Fertile Ejaculate. J Androl 16: 292–298.
    1. Fedder J (1996) Nonsperm cells in human semen: with special reference to seminal leukocytes and their possible influence on fertility. Arch Androl 36: 41–65.
    1. Tremellen K (2008) Oxidative Stress and male infertility – a clinical perspective. Hum Reprod Update 14: 243–258.
    1. Guo CJ, Wei JY, Yang J, Xu J, Pang W, et al. (2008) Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. Nutrition Research 28: 72–77.
    1. Hajimahmoodi M, Oveisi MR, Sadeghi N, Jannat B, Nateghi M (2009) Antioxidant capacity of plasma after pomegranate intake in human volunteer. Acta Medica Iranica 47: 125–132.
    1. Eslamian G, Amirjannati N, Rashidkhani B, Sadeghi MR, Hekmatdoost A (2012) Intake of food groups and idiopathic asthenozoospermia: a case-control study. Hum Reprod 27: 3328–3336.
    1. Zareba P, Colaci DS, Afeiche M, Gaskins AJ, Jørgensen N, et al. (2013) Semen quality in relation to antioxidant intake in e healthy male population. Fertil Steril 100: 1572–1579.
    1. Lombardo F, Sansone A, Romanelli F, Paoli D, Gandini L, et al. (2011) The role of antioxidant therapy in the treatment of male infertility: an overview. Asian J Androl 13: 690–696.
    1. Zini A, Al-Hathal N (2011) Antioxidant therapy in male infertility: Fact or fiction? Asian J Androl 13: 374–381.
    1. Gharagozloo P, Aitken RJ (2011) The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod 26: 1628–1640.
    1. Wirleitner B, Vanderzwalmen P, Stecher A, Spitzer D, Schuff M, et al. (2012) Dietary Supplementation of Antioxidants Improves Semen Quality of IVF Patients in Terms of Motility, Sperm Count, and Nuclear Vacuolization. Int J Vitam Nutr Res 82: 391–398.
    1. Khani B, Bidgoli SR, Hassani H (2013) Effect of sesame on sperm quality of infertile men. J Res Med Sci 18: 184–187.
    1. Dinkova-Kostova AT, Talalay P (2008) Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 52: S128–138.
    1. Birringer M (2011) Hormetics: dietary triggers of an adaptive stress response. Pharm Res 28: 2680–2694.
    1. Crozier A, Jaganath IB, Clifford MN (2009) Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 26: 1001–43.
    1. Satpathy S, Patra A, Purohit AP (2013) Estrogenic activity of Punica granatum L. peel extract. Asian Pacific Journal of Reproduction 2: 19–24.
    1. Miyauchi M, Nishikawa A, Furukawa F, Nakamura H, Son HY, et al. (2000) Inhibitory effects of 1′-acetoxychavicol acetate on N-nitrosobis(2-oxopropyl)-amine-induced initiation of cholangiocarcinogenesis in Syrian hamsters. Jpn J Cancer Res 91: 477–481.
    1. Nakamura Y, Miyoshi N (2010) Electrophiles in foods: the current status of isothiocyanates and their chemical biology. Biosci Biotechnol Biochem 74: 242–255.
    1. Yaku K, Matsui-Yuasa I, Azuma H, Kojima-Yuasa A (2011) 1′-Acetoxychavicol acetate enhances the phase II enzyme activities via the increase in intranuclear Nrf2 level and cytosolic p21 level. Amer J Chinese Med 39: 789–802.
    1. Yaku K, Matsui-Yuasa I, Konishi Y, Kojima-Yuasa A (2013) AMPK synergizes with the combined treatment of 1′-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities. Mol Nutr Food Res 57: 1198–1208.
    1. Higashida M, Xu S, Kojima-Yuasa A, Kennedy DO, Murakami A, et al. (2009) 1′-Acetoxychavicol acetate-induced cytotoxicity is accompanied by a rapid and drastic modulation of glutathione metabolism. Amino Acids 36: 107–113.
    1. Ando S, Matsuda H, Morikawa T, Yoshikawa M (2005) 1′S-1′-Acetoxychavicol acetate as a new type inhibitor of interferon-b production in lipopolysaccharide-activated mouse peritoneal macrophages. Bioorg Med Chem 13: 3289–3294.
    1. Ito K, Nakazato T, Ji Xian M, Yamada T, Hozumi N, et al. (2005) 1′-Acetoxychavicol acetate is a novel nuclear factor κB inhibitor with significant activity against multiple myeloma in vitro and in vivo. Cancer Res 65: 4417–4425.
    1. Lee CC, Houghton P (2005) Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer. J Ethnopharmacol 100: 237–243.
    1. Moffatt J, Hashimoto M, Kojima A, Kennedy DO, Murakami A, et al. (2000) Apoptosis induced by 1′-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation. Carcinogenesis 21: 2151–2157.
    1. Murakami A, Ohura S, Nakamura Y, Koshimizu K, Ohigashi H (1996) 1′-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin. Oncology 53: 386–391.
    1. Ohnishi M, Tanaka T, Makita H, Kawamori T, Mori H, et al. (1996) Chemopreventive effect of a xanthine oxidase inhibitor, 1′-acetoxychavicol acetate, on rat oral carcinogenesis. Jpn J Cancer Res 87: 349–356.

Source: PubMed

3
订阅