Oral Supplementation With AM3, Hesperidin and Spermidine Supplementation on Immunity Response and Biological Age.

NCT06249620 | Completed

• 1 other identifier: P21110b
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this interventional study is to know the immune status of healthy participants and to obtain their biological age before and after two months of ingesting a dietary supplement. These individuals are compared with others who will be given a product of similar appearance, but without containing active components, being the constituents of the placebo group. The study has a duration of 8 weeks, with 2 interventional visits (complete blood samples will be collected) at baseline and at 8 weeks. In order to be included in the trial, the patient must read the Patient Information Sheet and sign the informed consent form. The dosage regimen is two capsules per day in a single dose.

Conditions

Healthy

Keywords

AM3; Biological age; Inmunology clock; Spermidine; Hesperidin

Outcome Measures

Primary Outcomes (1)

• Change in Biological Age

  The Biological Age will be determined at baseline and week 8, by using the mathematical model 'Immunity Clock', based on the the natural killer activity, Lymphoproliferation and phagocytosis, and neutrophils and lymphocyts chemotaxis

  Baseline and Week 8

Secondary Outcomes (12)

• Change in catalase activity with the use of a spectrophotometer

  Baseline and week 8

• Change in Glutathione peroxidase levels

  Baseline and week 8

• Change in Glutathione reductase levels

  Baseline and week 8

• Change in reduced/oxized glutathione concentrations (GSH/GSSG)

  Baseline and week 8

• Change in inflammatory and anti-inflammatory cytokines levels

  Baseline and week 8

Study Arms (2)

Active group

EXPERIMENTAL

The product (with the active ingredients) is randomly given to 20 participants for ingestion for two months.The dosage regimen is two capsules per day in a single dose.

Dietary Supplement: Inmunoferon

Placebo

PLACEBO COMPARATOR

The other 20 participants will receive a similar looking product but with inert substances (placebo group).The dosage regimen is two capsules per day in a single dose.

Dietary Supplement: Placebo

Interventions

Inmunoferon DIETARY_SUPPLEMENT

The dosage regimen is two capsules (with the active ingredients) per day in a single dose.The study lasted 8 weeks, with 2 interventional visits at baseline and at 8 weeks. Blood samples are collected twice: once on day 0 of the study and again at the final visit.

Active group

Placebo DIETARY_SUPPLEMENT

The dosage regimen is two capsules (with inert ingredients) per day in a single dose.The study lasted 8 weeks, with 2 interventional visits at baseline and at 8 weeks. Blood samples are collected twice: once on day 0 of the study and again at the final visit.

Placebo

Eligibility Criteria

• Age: 29 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers who give their consent for the study will be included after having read and understood the information provided in the informed consent document
• Between 29-65 years old
• Residents in the Community of Madrid

You may not qualify if:

• Volunteers with no allergies or intolerances to the product
• Patologies
• Excessive alcohol consumption
• Pregnant women
• Antioxidants intake from supplements

Sponsors & Collaborators

• Industrial Farmacéutica Cantabria, S.A.: lead

Study Sites (1)

Facultad de Biología Universidad Complutense de Madrid

Madrid, 28040, Spain

Location

Related Publications (48)

• Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS. Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol. 1990 Mar;45(2):M45-8. doi: 10.1093/geronj/45.2.m45.

  PMID: 2313042 RESULT

• De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15(26):3003-26. doi: 10.2174/138161209789058110.

  PMID: 19754376 RESULT

• Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, Pletcher MA, Smith AE, Tang K, Yuan CW, Brown JC, Friedman J, He J, Heuton KR, Holmberg M, Patel DJ, Reidy P, Carter A, Cercy K, Chapin A, Douwes-Schultz D, Frank T, Goettsch F, Liu PY, Nandakumar V, Reitsma MB, Reuter V, Sadat N, Sorensen RJD, Srinivasan V, Updike RL, York H, Lopez AD, Lozano R, Lim SS, Mokdad AH, Vollset SE, Murray CJL. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018 Nov 10;392(10159):2052-2090. doi: 10.1016/S0140-6736(18)31694-5. Epub 2018 Oct 16.

  PMID: 30340847 RESULT

• Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990 Aug;65(3):375-98. doi: 10.1111/j.1469-185x.1990.tb01428.x. No abstract available.

  PMID: 2205304 RESULT

• HARMAN D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul;11(3):298-300. doi: 10.1093/geronj/11.3.298. No abstract available.

  PMID: 13332224 RESULT

• Martinez de Toda I, Mate I, Vida C, Cruces J, De la Fuente M. Immune function parameters as markers of biological age and predictors of longevity. Aging (Albany NY). 2016 Nov 28;8(11):3110-3119. doi: 10.18632/aging.101116.

  PMID: 27899767 RESULT

• Martinez de Toda I, Vida C, Diaz-Del Cerro E, De la Fuente M. The Immunity Clock. J Gerontol A Biol Sci Med Sci. 2021 Oct 13;76(11):1939-1945. doi: 10.1093/gerona/glab136.

  PMID: 33979432 RESULT

• Martinez de Toda I, Ceprian N, Diaz-Del Cerro E, De la Fuente M. The Role of Immune Cells in Oxi-Inflamm-Aging. Cells. 2021 Nov 1;10(11):2974. doi: 10.3390/cells10112974.

  PMID: 34831197 RESULT

• Arranz L, Fernandez C, Rodriguez A, Ribera JM, De la Fuente M. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med. 2008 Nov 1;45(9):1252-62. doi: 10.1016/j.freeradbiomed.2008.07.014. Epub 2008 Jul 27.

  PMID: 18694818 RESULT

• Maggini S, Pierre A, Calder PC. Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients. 2018 Oct 17;10(10):1531. doi: 10.3390/nu10101531.

  PMID: 30336639 RESULT

• Garrido A, Cruces J, Ceprian N, De la Fuente M. Improvements in Behavior and Immune Function and Increased Life Span of Old Mice Cohabiting With Adult Animals. J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):873-881. doi: 10.1093/gerona/gly043.

  PMID: 29506242 RESULT

• Rojo JM, Rejas MT, Ojeda G, Portoles P, Barasoain I. Enhancement of lymphocyte proliferation, interleukin-2 production and NK activity by inmunoferon (AM-3), a fungal immunomodulator: variations in normal and immunosuppressed mice. Int J Immunopharmacol. 1986;8(6):593-7. doi: 10.1016/0192-0561(86)90031-7.

  PMID: 3491798 RESULT

• Moya P, Baixeras E, Barasoain I, Rojo JM, Ronda E, Alonso ML, Portoles A. Immunoferon (AM3) enhances the activities of early-type interferon inducers and natural killer cells. Immunopharmacol Immunotoxicol. 1987;9(2-3):243-56. doi: 10.3109/08923978709035213.

  PMID: 2449486 RESULT

• Sanchez Palacios A, Garcia Marrero JA, Schamann F. [Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology]. Allergol Immunopathol (Madr). 1992 Jan-Feb;20(1):35-9. Spanish.

  PMID: 1509986 RESULT

• Villarrubia VG, Valladolid JM, Elorza FL, Sada G, Vilchez JG, Jimenez M, Herrerias JM. Therapeutic response of chronic active hepatitis B (CAHB) to a new immunomodulator: AM3. Immunohematological effects. Immunopharmacol Immunotoxicol. 1992;14(1-2):141-64. doi: 10.3109/08923979209009217.

  PMID: 1597653 RESULT

• Villarrubia VG, Moreno Koch MC, Calvo C, Gonzalez S, Alvarez-Mon M. The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3. Immunopharmacol Immunotoxicol. 1997 Feb;19(1):53-74. doi: 10.3109/08923979709038533.

  PMID: 9049659 RESULT

• Serrano-Gomez D, Martinez-Nunez RT, Sierra-Filardi E, Izquierdo N, Colmenares M, Pla J, Rivas L, Martinez-Picado J, Jimenez-Barbero J, Alonso-Lebrero JL, Gonzalez S, Corbi AL. AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN. Antimicrob Agents Chemother. 2007 Jul;51(7):2313-23. doi: 10.1128/AAC.01289-06. Epub 2007 Apr 23.

  PMID: 17452477 RESULT

• Martin-Vilchez S, Molina-Jimenez F, Alonso-Lebrero JL, Sanz-Cameno P, Rodriguez-Munoz Y, Benedicto I, Roda-Navarro P, Trapero M, Aragoneses-Fenoll L, Gonzalez S, Pivel JP, Corbi AL, Lopez-Cabrera M, Moreno-Otero R, Majano PL. AM3, a natural glycoconjugate, induces the functional maturation of human dendritic cells. Br J Pharmacol. 2008 Jun;154(3):698-708. doi: 10.1038/bjp.2008.87. Epub 2008 Apr 14.

  PMID: 18414382 RESULT

• Albillos A, Nieto M, Ubeda M, Munoz L, Fraile B, Reyes E, Lledo L, Blanco I, Pastor O, Salas C, Lario M, Monserrat J, Bataller R, Alvarez-Mon M. The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis. Gut. 2010 Jul;59(7):943-52. doi: 10.1136/gut.2008.168831. Epub 2010 May 4.

  PMID: 20442198 RESULT

• Yuan CL, Lin SW, Cheng MH. Inhibition of Molecular Signaling in Huh-7 Cells by AM3: A Novel Chemotherapeutic Agent for Hepatocellular Carcinoma. Med Chem. 2016;13(1):49-56. doi: 10.2174/1573406412666160622130036.

  PMID: 27342078 RESULT

• Fernandez-Lazaro D, Fernandez-Lazaro CI, Mielgo-Ayuso J, Adams DP, Garcia Hernandez JL, Gonzalez-Bernal J, Gonzalez-Gross M. Glycophosphopeptical AM3 Food Supplement: A Potential Adjuvant in the Treatment and Vaccination of SARS-CoV-2. Front Immunol. 2021 Jun 17;12:698672. doi: 10.3389/fimmu.2021.698672. eCollection 2021.

  PMID: 34220861 RESULT

• Larque E, Sabater-Molina M, Zamora S. Biological significance of dietary polyamines. Nutrition. 2007 Jan;23(1):87-95. doi: 10.1016/j.nut.2006.09.006. Epub 2006 Nov 20.

  PMID: 17113752 RESULT

• Ramani D, De Bandt JP, Cynober L. Aliphatic polyamines in physiology and diseases. Clin Nutr. 2014 Feb;33(1):14-22. doi: 10.1016/j.clnu.2013.09.019. Epub 2013 Oct 6.

  PMID: 24144912 RESULT

• Hesterberg RS, Cleveland JL, Epling-Burnette PK. Role of Polyamines in Immune Cell Functions. Med Sci (Basel). 2018 Mar 8;6(1):22. doi: 10.3390/medsci6010022.

  PMID: 29517999 RESULT

• Handa AK, Fatima T, Mattoo AK. Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease. Front Chem. 2018 Feb 5;6:10. doi: 10.3389/fchem.2018.00010. eCollection 2018.

  PMID: 29468148 RESULT

• Munoz-Esparza NC, Latorre-Moratalla ML, Comas-Baste O, Toro-Funes N, Veciana-Nogues MT, Vidal-Carou MC. Polyamines in Food. Front Nutr. 2019 Jul 11;6:108. doi: 10.3389/fnut.2019.00108. eCollection 2019.

  PMID: 31355206 RESULT

• Ramos-Molina B, Queipo-Ortuno MI, Lambertos A, Tinahones FJ, Penafiel R. Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases. Front Nutr. 2019 Mar 14;6:24. doi: 10.3389/fnut.2019.00024. eCollection 2019.

  PMID: 30923709 RESULT

• Nakanishi S, Cleveland JL. Polyamine Homeostasis in Development and Disease. Med Sci (Basel). 2021 May 13;9(2):28. doi: 10.3390/medsci9020028.

  PMID: 34068137 RESULT

• Sagar NA, Tarafdar S, Agarwal S, Tarafdar A, Sharma S. Polyamines: Functions, Metabolism, and Role in Human Disease Management. Med Sci (Basel). 2021 Jun 9;9(2):44. doi: 10.3390/medsci9020044.

  PMID: 34207607 RESULT

• Negrel S, Brunel JM. Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview. Curr Med Chem. 2021;28(17):3406-3448. doi: 10.2174/0929867327666201102114544.

  PMID: 33138746 RESULT

• Bravo-San Pedro JM, Senovilla L. Immunostimulatory activity of lifespan-extending agents. Aging (Albany NY). 2013 Nov;5(11):793-801. doi: 10.18632/aging.100619.

  PMID: 24389041 RESULT

• Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788.

  PMID: 29371440 RESULT

• Stacchiotti A, Corsetti G. Natural Compounds and Autophagy: Allies Against Neurodegeneration. Front Cell Dev Biol. 2020 Sep 22;8:555409. doi: 10.3389/fcell.2020.555409. eCollection 2020.

  PMID: 33072744 RESULT

• Soda K. Spermine and gene methylation: a mechanism of lifespan extension induced by polyamine-rich diet. Amino Acids. 2020 Feb;52(2):213-224. doi: 10.1007/s00726-019-02733-2. Epub 2019 Apr 19.

  PMID: 31004229 RESULT

• Zhang M, Wang H, Tracey KJ. Regulation of macrophage activation and inflammation by spermine: a new chapter in an old story. Crit Care Med. 2000 Apr;28(4 Suppl):N60-6. doi: 10.1097/00003246-200004001-00007.

  PMID: 10807317 RESULT

• Proietti E, Rossini S, Grohmann U, Mondanelli G. Polyamines and Kynurenines at the Intersection of Immune Modulation. Trends Immunol. 2020 Nov;41(11):1037-1050. doi: 10.1016/j.it.2020.09.007. Epub 2020 Oct 12.

  PMID: 33055013 RESULT

• Zhang H, Simon AK. Polyamines reverse immune senescence via the translational control of autophagy. Autophagy. 2020 Jan;16(1):181-182. doi: 10.1080/15548627.2019.1687967. Epub 2019 Nov 6.

  PMID: 31679458 RESULT

• Latour YL, Gobert AP, Wilson KT. The role of polyamines in the regulation of macrophage polarization and function. Amino Acids. 2020 Feb;52(2):151-160. doi: 10.1007/s00726-019-02719-0. Epub 2019 Apr 23.

  PMID: 31016375 RESULT

• Barreca D, Gattuso G, Bellocco E, Calderaro A, Trombetta D, Smeriglio A, Lagana G, Daglia M, Meneghini S, Nabavi SM. Flavanones: Citrus phytochemical with health-promoting properties. Biofactors. 2017 Jul 8;43(4):495-506. doi: 10.1002/biof.1363. Epub 2017 May 12.

  PMID: 28497905 RESULT

• Mas-Capdevila A, Teichenne J, Domenech-Coca C, Caimari A, Del Bas JM, Escote X, Crescenti A. Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability. Nutrients. 2020 May 20;12(5):1488. doi: 10.3390/nu12051488.

  PMID: 32443766 RESULT

• Xiong H, Wang J, Ran Q, Lou G, Peng C, Gan Q, Hu J, Sun J, Yao R, Huang Q. Hesperidin: A Therapeutic Agent For Obesity. Drug Des Devel Ther. 2019 Nov 12;13:3855-3866. doi: 10.2147/DDDT.S227499. eCollection 2019.

  PMID: 32009777 RESULT

• Tejada S, Pinya S, Martorell M, Capo X, Tur JA, Pons A, Sureda A. Potential Anti-inflammatory Effects of Hesperidin from the Genus Citrus. Curr Med Chem. 2018;25(37):4929-4945. doi: 10.2174/0929867324666170718104412.

  PMID: 28721824 RESULT

• Hajialyani M, Hosein Farzaei M, Echeverria J, Nabavi SM, Uriarte E, Sobarzo-Sanchez E. Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules. 2019 Feb 12;24(3):648. doi: 10.3390/molecules24030648.

  PMID: 30759833 RESULT

• Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Crit Rev Food Sci Nutr. 2017 Feb 11;57(3):613-631. doi: 10.1080/10408398.2014.906382.

  PMID: 25675136 RESULT

• Estruel-Amades S, Massot-Cladera M, Perez-Cano FJ, Franch A, Castell M, Camps-Bossacoma M. Hesperidin Effects on Gut Microbiota and Gut-Associated Lymphoid Tissue in Healthy Rats. Nutrients. 2019 Feb 2;11(2):324. doi: 10.3390/nu11020324.

  PMID: 30717392 RESULT

• Camps-Bossacoma M, Franch A, Perez-Cano FJ, Castell M. Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response. Nutrients. 2017 Jun 6;9(6):580. doi: 10.3390/nu9060580.

  PMID: 28587283 RESULT

• Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Hesperidin Supplementation Alleviates Oxidative DNA Damage and Lipid Peroxidation in Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Phytother Res. 2017 Oct;31(10):1539-1545. doi: 10.1002/ptr.5881. Epub 2017 Aug 14.

  PMID: 28805022 RESULT

• Li Y, Kandhare AD, Mukherjee AA, Bodhankar SL. Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats. Regul Toxicol Pharmacol. 2019 Jul;105:77-85. doi: 10.1016/j.yrtph.2019.04.001. Epub 2019 Apr 13.

  PMID: 30991075 RESULT

Related Links

• Oxidation and Inflammation in the Immune and Nervous Systems, a Link Between Aging and Anxiety
• Estrategias para enlentecer el envejecimiento en modelos de ratón y en humanos. Efectos sobre la longevidad y la edad biológica

MeSH Terms

Interventions

Immunoferon

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2023
• First Posted: February 8, 2024
• Study Start: April 19, 2022
• Primary Completion: July 11, 2022
• Study Completion: October 1, 2022
• Last Updated: February 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)