Interim report from a 2-year double-blind rct testing fermented papaya preparation on immune enhancement, endothelial health and qol in elderly adults

Abstract

Background: Agingis associated with alterations in oxi-inflammatory-immune profile, and endothelial cell dysfunction. Indeed, increased generation of free radicals as well as immunosenescence are hallmarks of the aging process and age-related diseases. In the past 12 years or so, data has been accumulated on fermented papaya preparation (FPP®)(Osato Research Institute, Gifu, Japan), a specific functional food with robust redox and immune regulator nutrigenomics effect. The aim of this 2-year ongoing study of which we report the first-year data, was to test FPP® in redox, endothelial, and immune markers.Methods: Study population. From a total of 106 subjects, we report the analyzed data referring to 78 clinically stable, healthy, community-dwelling males and females, aged 60 to 75 years. The study was conducted using a double-blind method with designated groups A and B to fulfill the two different treatments. The two treatments are as follows: Group A, also known as “FPP Group,” was given one sachet two times per day containing 4.5g FPP®, along with one placebo capsule provided in the morning. Group B, also known as “AA Group,” was given one papaya-flavored sachet two times per day, along with one antioxidant mixture capsule in the morning. Morning blood samples were collected and tested for: Ultra-sensitive c-reactive protein (a highly sensitive ELISA), inducible nitric oxide synthase (iNOS) (by Human Nitric Oxide Synthase kit), asymmetric dimethylarginine, or ADMA, (a competitive enzyme-linked immunosorbent assay), apoptosis of PBMCs (by Annexin V staining) and MOS 36-item short-form health survey (SF-36) to assess quality of life. Screening and blood tests were carried out as follows: Visit I: Day 0 - Baseline, Visit II: Day 60, or 2 months, Visit III: 6 months, Visit IV: 11 months.Results: Plasma iNOS levels were comparable among both groups at the beginning of the study. FPP®-treated subjects showed a significant increased level at Visits II and III (P<0.05 vs baseline and vs AA). ADMA values were not affected by AA supplementation whereas FPP® treatment was associated with a significant decrease beginning with observation during Visit III (P<0.05 vs baseline and vs AA administration). The FPP® intervention was associated with improvements among several domains of quality of life such as physical function, general health, and mental components (P < 0.01 vs baseline and vs AA group). There was also at significant and comparable positive effect for time on vitality shown in both AA and FPP® groups.Conclusion: Unlike with the antioxidant treatment, the FPP® intervention yielded a transient decrease of ADMA, a decrease of iNOS and lower percentage in apoptotic PBMC. These results suggest that FPP®, by a more multifaceted, subcellular mechanism, as well as non-redox modulatory properties, was beneficially effective in regulating aging markers. These mechanisms are associated with a better SF-36 profile in support of FPP® as a candidate interventional functional food for health maintenance, and specifically in middle-age/elderly subjects.Keywords: Fermented Papaya Preparation, Nitric oxide, ADMA, apoptosis, antioxidants, SF-36

Effects of dietary supplementation with fermented papaya on oxidative stress, symptoms, and microbiome in Parkinson's disease

“…Some studies on chronic degenerative diseases such as thalassemia, cirrhosis, diabetes as well as aging have shown that FPP can act favorably on the immune and vascular systems through an anti-inflammatory action and a modification of the biomarkers of oxidative stress damage [59][60][61][62]. For these positive direct and indirect effects on health, FPP is considered a functional food [63][64].…”

Neutrophil-lymphocyte ratio and update conclusions from a 2-year double-blind rct testing fermented papaya preparation in healthy middle-aged/elderly subjects

“…For the last 13 years, a proprietary functional food known as fermented papaya preparation (FPP®, Osato Research Institute, Gifu, Japan, Patent Number: 6401792) has undergone rigorous validation through numerous experimental and clinical trials, showcasing its enduring immune and redox modulator nutrigenomics effects [1][2][3][4][5][6].The Functional Food Center's (FFC) recent consensus has provided a distinct and enhanced definition for evidence-based functional foods, elucidating their impactful bioactivity and the associated biomarkers [7].This year a brief but stringent position paper further focused on the fundamental regulatory pillars in the field [8]. In the previously published 1-year preliminary report [9] of the present 2-year investigation, we demonstrated that, as compared to the antioxidant-mix supplementation, FPP ® intervention significantly decreased the asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor and the percentage of apoptotic PBMC, together with a more satisfactory quality of life profile in middle-age/elderly subjects. On the other hand, the dynamics of other variables such as neutrophil lymphocyte ratio (NLR) values, no matter the treatment group, did not reach substantial differences.…”

Pharmacokinetic effect of Astragalus membranaceus and Panax notoginseng saponins on arginine absorption and nitric oxide production in healthy subjects

“…Since cGMP is excreted through urine, measuring the levels of urinary nitrates Functional Foods in Health and Disease 2023; 13 (6):307-319 and cGMP is a suitable and non-invasive method for assessing NO. Asymmetric dimethylarginine (ADMA) is widely recognized as the inhibitor of NO production by competing for the binding with arginine and NO synthase (NOS) [6][7]. Therefore, the ratio of arginine/ADMA (substrate/inhibitor ratio) may predict NO production better than ADMA or arginine concentrations alone [8].…”