<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03005847</url>
  </required_header>
  <id_info>
    <org_study_id>FPP001-HMO-CTIL</org_study_id>
    <nct_id>NCT03005847</nct_id>
  </id_info>
  <brief_title>The Effect of Fermented Papaya Preparation on Patients With Chronic Kidney Disease Under Dialysis Receiving Intravenous Iron</brief_title>
  <official_title>The Effect of Fermented Papaya Preparation on Patients With Chronic Kidney Disease Under Dialysis Receiving Intravenous Iron</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hadassah Medical Organization</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hadassah Medical Organization</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fermented papaya preparation has been reported to bind and neutralize reactive oxygen species&#xD;
      as well as iron. Patients undergoing hemodialysis are generally on iron overload status due&#xD;
      to their inability to use iron storage adequately. The aim of this study is to evaluate the&#xD;
      effect of FPP on the iron status of these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background and rationale&#xD;
&#xD;
      Patients with chronic kidney disease (CKD) on hemodialysis often suffer from anemia. The&#xD;
      anemia is primarily caused by insufficient production by the failing kidneys of the erythroid&#xD;
      stimulating hormone - erythropoietin (Epo). Oxidative stress may be another reason for&#xD;
      anemia. Oxidative stress in RBCs of these patients may be caused by:&#xD;
&#xD;
        1. Passage of the blood through the plastic tubing during the dialysis procedure. We have&#xD;
           shown oxidative stress in RBCs following passage of blood through similar tubing during&#xD;
           leukopheresis procedure (1). Other groups reported similar effects during hemodialysis.&#xD;
&#xD;
        2. Iron overload - In order to maximize the effect of Epo, the treatment is supplemented by&#xD;
           IV injection of iron. This iron may accumulate and cause iron overload in some&#xD;
           hemodialyzed patients. Under normal conditions, iron is transported in the blood and&#xD;
           enters into cells following binding the plasma protein transferrin. However, when iron&#xD;
           content in the plasma exceeds the binding capacity of transferrin, non-transferrin-bound&#xD;
           iron (NTBI) appears. This iron enters cells via alternative pathways, and accumulates in&#xD;
           the cytosol, where it participates in chemical reactions (Haber-Weiss, Fenton) that&#xD;
           generate reactive oxygen species (ROS). Excess ROS overcomes the protective cellular&#xD;
           anti-oxidant mechanisms and becomes cytotoxic. In the erythroid system, excess ROS&#xD;
           causes accelerated apoptosis (programmed cell death) of precursor cells in the bone&#xD;
           marrow and a short survival of mature RBCs in the circulation, resulting in chronic&#xD;
           anemia. Excess iron and ROS may also damage other cells and lead to malfunctioning of&#xD;
           vital organs, such as the heart and liver (2,3).&#xD;
&#xD;
           FPP has been reported to bind and neutralize (scavenge) ROS (4) as well as free iron&#xD;
           (chelate) (5). Both activities ameliorate the oxidative stress.&#xD;
&#xD;
           Treatment with FPP of various diseases associated with oxidative stress, administered&#xD;
           orally (3 gr. X 3 times a day), have been shown to significantly ameliorate the symptoms&#xD;
           underlying these diseases (6-18). FPP has a long track-record of safe human consumption&#xD;
           (19-20). It has been used for many years as a food-supplement by thousands of people&#xD;
           around the world without any reported side effect.&#xD;
&#xD;
           Research goals&#xD;
&#xD;
           To study the effect of fermented papaya preparation (FPP) on patients with chronic&#xD;
           kidney disease (CKD) under dialysis, receiving intravenous iron.&#xD;
&#xD;
           General Protocol:&#xD;
&#xD;
           This will be a single-arm, open-label, single-center study in 20 patients upon dialysis&#xD;
           receiving IV iron supplementation. All participants will be treated with FPP for 3&#xD;
           months.&#xD;
&#xD;
           Bi-weekly, blood samples will be drawn and the patients will be monitored for assessment&#xD;
           of safety and efficacy.&#xD;
&#xD;
           Detailed Protocol Twenty patients, treated on Hadassah Medical center, Jerusalem, will&#xD;
           be screened and recruited according to clinical criteria.&#xD;
&#xD;
           inclusion criteria: Age 18-70. Any primary kidney disease resulting in ESRD.&#xD;
           Hemodynamically stable status. PTH up to 2-9 times upper normal limits. Patients&#xD;
           receiving ESA may be included.&#xD;
&#xD;
        3. Exclusion criteria:&#xD;
&#xD;
      Any evidence of acute bleeding. Hg level of less than 8 g/dL Patients with known allergy to&#xD;
      Papaya&#xD;
&#xD;
      3. Patients will be treated orally with FPP (3 gr. X 3 times a day) for 3 months.&#xD;
&#xD;
      4. Blood samples will be obtained from all patients prior and during (every 2 weeks)&#xD;
      treatment.&#xD;
&#xD;
      5. Samples will be analyzed for:&#xD;
&#xD;
      Blood chemistry for Potassium, Albumin and Phosphorous (every 2 weeks).&#xD;
&#xD;
      Anemia: Complete blood count, including RBC number and indexes, as well as hemoglobin&#xD;
      content.&#xD;
&#xD;
      Oxidative stress: (once monthly) Reactive oxygen species Reduced glutathione Membrane lipid&#xD;
      peroxidation External phosphatidylserine&#xD;
&#xD;
      Iron overload: (once monthly) Serum ferritin Serum transferin. Labile plasma iron Serum&#xD;
      hepcidin Intracellular labile iron pool&#xD;
&#xD;
      Safety measures:&#xD;
&#xD;
      Adverse events: Frequency, severity, seriousness, time to onset, duration, and relatedness to&#xD;
      study product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>March 2017</start_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Iron status</measure>
    <time_frame>3 months of treatment</time_frame>
    <description>evaluation of iron overload reduction after 3 months of treatment with fermented papaya preparation</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Anemia</condition>
  <condition>Chronic Kidney Disease Stage 5</condition>
  <arm_group>
    <arm_group_label>FPP arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>active treatment with fermented papaya preparation</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>fermented papaya preparation</intervention_name>
    <description>dietary supplementation with fermented papaya preparation</description>
    <arm_group_label>FPP arm</arm_group_label>
    <other_name>FPP</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70. Any primary kidney disease resulting in ESRD. Hemodynamically stable&#xD;
             status. PTH up to 2-9 times upper normal limits. Patients receiving ESA may be&#xD;
             included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any evidence of acute bleeding. Hg level of less than 8 g/dL Patients with known&#xD;
             allergy to Papaya&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>itamar sagiv, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Medical Organization</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Itamar Sagiv, MD</last_name>
    <phone>97226776881</phone>
    <email>itamar@hadassah.org.il</email>
  </overall_contact>
  <reference>
    <citation>Amer J, Frankenburg S, Fibach E. Apheresis induces oxidative stress in blood cells. Ther Apher Dial. 2010 Apr;14(2):166-71. doi: 10.1111/j.1744-9987.2009.00746.x.</citation>
    <PMID>20438538</PMID>
  </reference>
  <reference>
    <citation>Ghoti H, Rachmilewitz EA, Simon-Lopez R, Gaber R, Katzir Z, Konen E, Kushnir T, Girelli D, Campostrini N, Fibach E, Goitein O. Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol. 2012 Jul;89(1):87-93. doi: 10.1111/j.1600-0609.2012.01783.x. Epub 2012 May 18.</citation>
    <PMID>22435497</PMID>
  </reference>
  <reference>
    <citation>Gaweda AE, Ginzburg YZ, Chait Y, Germain MJ, Aronoff GR, Rachmilewitz E. Iron dosing in kidney disease: inconsistency of evidence and clinical practice. Nephrol Dial Transplant. 2015 Feb;30(2):187-96. doi: 10.1093/ndt/gfu104. Epub 2014 May 12.</citation>
    <PMID>24821751</PMID>
  </reference>
  <reference>
    <citation>Amer J, Goldfarb A, Rachmilewitz EA, Fibach E. Fermented papaya preparation as redox regulator in blood cells of beta-thalassemic mice and patients. Phytother Res. 2008 Jun;22(6):820-8. doi: 10.1002/ptr.2379.</citation>
    <PMID>18384199</PMID>
  </reference>
  <reference>
    <citation>Prus E, Fibach E. The antioxidant effect of fermented papaya preparation involves iron chelation. J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2):203-10.</citation>
    <PMID>22824747</PMID>
  </reference>
  <reference>
    <citation>Bertuccelli G, Marotta F, Zerbinati N, Cabeca A, He F, Jain S, Lorenzetti A, Yadav H, Milazzo M, Calabrese F, Tomella C, Catanzaro R. Iron supplementation in young iron-deficient females causes gastrointestinal redox imbalance: protective effect of a fermented nutraceutical. J Biol Regul Homeost Agents. 2014 Jan-Mar;28(1):53-63.</citation>
    <PMID>24750791</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Naito Y, Jain S, Lorenzetti A, Soresi V, Kumari A, Carrera Bastos P, Tomella C, Yadav H. Is there a potential application of a fermented nutraceutical in acute respiratory illnesses? An in-vivo placebo-controlled, cross-over clinical study in different age groups of healthy subjects. J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2):285-94.</citation>
    <PMID>22824755</PMID>
  </reference>
  <reference>
    <citation>Somanah J, Aruoma OI, Gunness TK, Kowelssur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J, Bourdon E, Bahorun T. Effects of a short term supplementation of a fermented papaya preparation on biomarkers of diabetes mellitus in a randomized Mauritian population. Prev Med. 2012 May;54 Suppl:S90-7. doi: 10.1016/j.ypmed.2012.01.014. Epub 2012 Feb 11.</citation>
    <PMID>22330753</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Chui DH, Jain S, Polimeni A, Koike K, Zhou L, Lorenzetti A, Shimizu H, Yang H. Effect of a fermented nutraceutical on thioredoxin level and TNF-alpha signalling in cirrhotic patients. J Biol Regul Homeost Agents. 2011 Jan-Mar;25(1):37-45.</citation>
    <PMID>21382272</PMID>
  </reference>
  <reference>
    <citation>Ghoti H, Fibach E, Dana M, Abu Shaban M, Jeadi H, Braester A, Matas Z, Rachmilewitz E. Oxidative stress contributes to hemolysis in patients with hereditary spherocytosis and can be ameliorated by fermented papaya preparation. Ann Hematol. 2011 May;90(5):509-13. doi: 10.1007/s00277-010-1110-2. Epub 2010 Nov 10.</citation>
    <PMID>21063708</PMID>
  </reference>
  <reference>
    <citation>Aruoma OI, Hayashi Y, Marotta F, Mantello P, Rachmilewitz E, Montagnier L. Applications and bioefficacy of the functional food supplement fermented papaya preparation. Toxicology. 2010 Nov 28;278(1):6-16. doi: 10.1016/j.tox.2010.09.006. Epub 2010 Sep 24.</citation>
    <PMID>20870007</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Koike K, Lorenzetti A, Jain S, Signorelli P, Metugriachuk Y, Mantello P, Locorotondo N. Regulating redox balance gene expression in healthy individuals by nutraceuticals: a pilot study. Rejuvenation Res. 2010 Apr-Jun;13(2-3):175-8. doi: 10.1089/rej.2009.0950.</citation>
    <PMID>20370494</PMID>
  </reference>
  <reference>
    <citation>Fibach E, Tan ES, Jamuar S, Ng I, Amer J, Rachmilewitz EA. Amelioration of oxidative stress in red blood cells from patients with beta-thalassemia major and intermedia and E-beta-thalassemia following administration of a fermented papaya preparation. Phytother Res. 2010 Sep;24(9):1334-8. doi: 10.1002/ptr.3116.</citation>
    <PMID>20127662</PMID>
  </reference>
  <reference>
    <citation>Ghoti H, Rosenbaum H, Fibach E, Rachmilewitz EA. Decreased hemolysis following administration of antioxidant-fermented papaya preparation (FPP) to a patient with PNH. Ann Hematol. 2010 Apr;89(4):429-30. doi: 10.1007/s00277-009-0821-8. Epub 2009 Sep 15. No abstract available.</citation>
    <PMID>19756600</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Yoshida C, Barreto R, Naito Y, Packer L. Oxidative-inflammatory damage in cirrhosis: effect of vitamin E and a fermented papaya preparation. J Gastroenterol Hepatol. 2007 May;22(5):697-703. doi: 10.1111/j.1440-1746.2007.04937.x.</citation>
    <PMID>17444858</PMID>
  </reference>
  <reference>
    <citation>Danese C, Esposito D, D'Alfonso V, Cirene M, Ambrosino M, Colotto M. Plasma glucose level decreases as collateral effect of fermented papaya preparation use. Clin Ter. 2006 May-Jun;157(3):195-8.</citation>
    <PMID>16900843</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Weksler M, Naito Y, Yoshida C, Yoshioka M, Marandola P. Nutraceutical supplementation: effect of a fermented papaya preparation on redox status and DNA damage in healthy elderly individuals and relationship with GSTM1 genotype: a randomized, placebo-controlled, cross-over study. Ann N Y Acad Sci. 2006 May;1067:400-7. doi: 10.1196/annals.1354.057.</citation>
    <PMID>16804018</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Barreto R, Tajiri H, Bertuccelli J, Safran P, Yoshida C, Fesce E. The aging/precancerous gastric mucosa: a pilot nutraceutical trial. Ann N Y Acad Sci. 2004 Jun;1019:195-9. doi: 10.1196/annals.1297.031.</citation>
    <PMID>15247013</PMID>
  </reference>
  <reference>
    <citation>Marotta F, Koike K, Lorenzetti A, Naito Y, Fayet F, Shimizu H, Marandola P. Nutraceutical strategy in aging: targeting heat shock protein and inflammatory profile through understanding interleukin-6 polymorphism. Ann N Y Acad Sci. 2007 Nov;1119:196-202. doi: 10.1196/annals.1404.011.</citation>
    <PMID>18056967</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 26, 2016</study_first_submitted>
  <study_first_submitted_qc>December 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hadassah Medical Organization</investigator_affiliation>
    <investigator_full_name>Itamr Sagiv</investigator_full_name>
    <investigator_title>primary investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03005847
org study id: FPP001-HMO-CTIL
nct id: NCT03005847
lead sponsor: 
has dmc: No
Fermented papaya preparation has been reported to bind and neutralize reactive oxygen species
      as well as iron. Patients undergoing hemodialysis are generally on iron overload status due
      to their inability to use iron storage adequately. The aim of this study is to evaluate the
      effect of FPP on the iron status of these patients.
Background and rationale

      Patients with chronic kidney disease (CKD) on hemodialysis often suffer from anemia. The
      anemia is primarily caused by insufficient production by the failing kidneys of the erythroid
      stimulating hormone - erythropoietin (Epo). Oxidative stress may be another reason for
      anemia. Oxidative stress in RBCs of these patients may be caused by:

        1. Passage of the blood through the plastic tubing during the dialysis procedure. We have
           shown oxidative stress in RBCs following passage of blood through similar tubing during
           leukopheresis procedure (1). Other groups reported similar effects during hemodialysis.

        2. Iron overload - In order to maximize the effect of Epo, the treatment is supplemented by
           IV injection of iron. This iron may accumulate and cause iron overload in some
           hemodialyzed patients. Under normal conditions, iron is transported in the blood and
           enters into cells following binding the plasma protein transferrin. However, when iron
           content in the plasma exceeds the binding capacity of transferrin, non-transferrin-bound
           iron (NTBI) appears. This iron enters cells via alternative pathways, and accumulates in
           the cytosol, where it participates in chemical reactions (Haber-Weiss, Fenton) that
           generate reactive oxygen species (ROS). Excess ROS overcomes the protective cellular
           anti-oxidant mechanisms and becomes cytotoxic. In the erythroid system, excess ROS
           causes accelerated apoptosis (programmed cell death) of precursor cells in the bone
           marrow and a short survival of mature RBCs in the circulation, resulting in chronic
           anemia. Excess iron and ROS may also damage other cells and lead to malfunctioning of
           vital organs, such as the heart and liver (2,3).

           FPP has been reported to bind and neutralize (scavenge) ROS (4) as well as free iron
           (chelate) (5). Both activities ameliorate the oxidative stress.

           Treatment with FPP of various diseases associated with oxidative stress, administered
           orally (3 gr. X 3 times a day), have been shown to significantly ameliorate the symptoms
           underlying these diseases (6-18). FPP has a long track-record of safe human consumption
           (19-20). It has been used for many years as a food-supplement by thousands of people
           around the world without any reported side effect.

           Research goals

           To study the effect of fermented papaya preparation (FPP) on patients with chronic
           kidney disease (CKD) under dialysis, receiving intravenous iron.

           General Protocol:

           This will be a single-arm, open-label, single-center study in 20 patients upon dialysis
           receiving IV iron supplementation. All participants will be treated with FPP for 3
           months.

           Bi-weekly, blood samples will be drawn and the patients will be monitored for assessment
           of safety and efficacy.

           Detailed Protocol Twenty patients, treated on Hadassah Medical center, Jerusalem, will
           be screened and recruited according to clinical criteria.

           inclusion criteria: Age 18-70. Any primary kidney disease resulting in ESRD.
           Hemodynamically stable status. PTH up to 2-9 times upper normal limits. Patients
           receiving ESA may be included.

        3. Exclusion criteria:

      Any evidence of acute bleeding. Hg level of less than 8 g/dL Patients with known allergy to
      Papaya

      3. Patients will be treated orally with FPP (3 gr. X 3 times a day) for 3 months.

      4. Blood samples will be obtained from all patients prior and during (every 2 weeks)
      treatment.

      5. Samples will be analyzed for:

      Blood chemistry for Potassium, Albumin and Phosphorous (every 2 weeks).

      Anemia: Complete blood count, including RBC number and indexes, as well as hemoglobin
      content.

      Oxidative stress: (once monthly) Reactive oxygen species Reduced glutathione Membrane lipid
      peroxidation External phosphatidylserine

      Iron overload: (once monthly) Serum ferritin Serum transferin. Labile plasma iron Serum
      hepcidin Intracellular labile iron pool

      Safety measures:

      Adverse events: Frequency, severity, seriousness, time to onset, duration, and relatedness to
      study product.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Iron status
time frame: 3 months of treatment
description: evaluation of iron overload reduction after 3 months of treatment with fermented papaya preparation
arm group label: FPP arm
arm group type: Experimental
description: active treatment with fermented papaya preparation
intervention type: Dietary Supplement
intervention name: fermented papaya preparation
description: dietary supplementation with fermented papaya preparation
arm group label: FPP arm
other name: FPP
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: itamar sagiv, MD
role: Principal Investigator
affiliation: Hadassah Medical Organization
last name: Itamar Sagiv, MD
phone: 97226776881
email: itamar@hadassah.org.il
citation: Amer J, Frankenburg S, Fibach E. Apheresis induces oxidative stress in blood cells. Ther Apher Dial. 2010 Apr;14(2):166-71. doi: 10.1111/j.1744-9987.2009.00746.x.
PMID: 20438538
citation: Ghoti H, Rachmilewitz EA, Simon-Lopez R, Gaber R, Katzir Z, Konen E, Kushnir T, Girelli D, Campostrini N, Fibach E, Goitein O. Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol. 2012 Jul;89(1):87-93. doi: 10.1111/j.1600-0609.2012.01783.x. Epub 2012 May 18.
PMID: 22435497
citation: Gaweda AE, Ginzburg YZ, Chait Y, Germain MJ, Aronoff GR, Rachmilewitz E. Iron dosing in kidney disease: inconsistency of evidence and clinical practice. Nephrol Dial Transplant. 2015 Feb;30(2):187-96. doi: 10.1093/ndt/gfu104. Epub 2014 May 12.
PMID: 24821751
citation: Amer J, Goldfarb A, Rachmilewitz EA, Fibach E. Fermented papaya preparation as redox regulator in blood cells of beta-thalassemic mice and patients. Phytother Res. 2008 Jun;22(6):820-8. doi: 10.1002/ptr.2379.
PMID: 18384199
citation: Prus E, Fibach E. The antioxidant effect of fermented papaya preparation involves iron chelation. J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2):203-10.
PMID: 22824747
citation: Bertuccelli G, Marotta F, Zerbinati N, Cabeca A, He F, Jain S, Lorenzetti A, Yadav H, Milazzo M, Calabrese F, Tomella C, Catanzaro R. Iron supplementation in young iron-deficient females causes gastrointestinal redox imbalance: protective effect of a fermented nutraceutical. J Biol Regul Homeost Agents. 2014 Jan-Mar;28(1):53-63.
PMID: 24750791
citation: Marotta F, Naito Y, Jain S, Lorenzetti A, Soresi V, Kumari A, Carrera Bastos P, Tomella C, Yadav H. Is there a potential application of a fermented nutraceutical in acute respiratory illnesses? An in-vivo placebo-controlled, cross-over clinical study in different age groups of healthy subjects. J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2):285-94.
PMID: 22824755
citation: Somanah J, Aruoma OI, Gunness TK, Kowelssur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J, Bourdon E, Bahorun T. Effects of a short term supplementation of a fermented papaya preparation on biomarkers of diabetes mellitus in a randomized Mauritian population. Prev Med. 2012 May;54 Suppl:S90-7. doi: 10.1016/j.ypmed.2012.01.014. Epub 2012 Feb 11.
PMID: 22330753
citation: Marotta F, Chui DH, Jain S, Polimeni A, Koike K, Zhou L, Lorenzetti A, Shimizu H, Yang H. Effect of a fermented nutraceutical on thioredoxin level and TNF-alpha signalling in cirrhotic patients. J Biol Regul Homeost Agents. 2011 Jan-Mar;25(1):37-45.
PMID: 21382272
citation: Ghoti H, Fibach E, Dana M, Abu Shaban M, Jeadi H, Braester A, Matas Z, Rachmilewitz E. Oxidative stress contributes to hemolysis in patients with hereditary spherocytosis and can be ameliorated by fermented papaya preparation. Ann Hematol. 2011 May;90(5):509-13. doi: 10.1007/s00277-010-1110-2. Epub 2010 Nov 10.
PMID: 21063708
citation: Aruoma OI, Hayashi Y, Marotta F, Mantello P, Rachmilewitz E, Montagnier L. Applications and bioefficacy of the functional food supplement fermented papaya preparation. Toxicology. 2010 Nov 28;278(1):6-16. doi: 10.1016/j.tox.2010.09.006. Epub 2010 Sep 24.
PMID: 20870007
citation: Marotta F, Koike K, Lorenzetti A, Jain S, Signorelli P, Metugriachuk Y, Mantello P, Locorotondo N. Regulating redox balance gene expression in healthy individuals by nutraceuticals: a pilot study. Rejuvenation Res. 2010 Apr-Jun;13(2-3):175-8. doi: 10.1089/rej.2009.0950.
PMID: 20370494
citation: Fibach E, Tan ES, Jamuar S, Ng I, Amer J, Rachmilewitz EA. Amelioration of oxidative stress in red blood cells from patients with beta-thalassemia major and intermedia and E-beta-thalassemia following administration of a fermented papaya preparation. Phytother Res. 2010 Sep;24(9):1334-8. doi: 10.1002/ptr.3116.
PMID: 20127662
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PMID: 19756600
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PMID: 16804018
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PMID: 18056967
responsible party type: Principal Investigator
investigator affiliation: Hadassah Medical Organization
investigator full name: Itamr Sagiv
investigator title: primary investigator
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: No