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


  • Aldo Lorenzetti
  • Antonio Ayala
  • Fang He
  • Cristiana Aperio
  • Leila Haghshenas
  • Maki Osato
  • Umberto Solimene
  • Saida Rasulova
  • Francesco Marotta



Background:T his study represents the second part of a 2-year interventional study in middle-aged /elderly healthy subjects treated either with an antioxidant supplementation (200mg trans-resveratrol, 100mg Centella asiatica extract, 80mg ubiquinol, 50mg epigallo-cathechin-gallate, 20 mg anthocyanidins, 5mg zinc, and 200 IU vitamin E) or with a proprietary fermented papaya preparation (FPP). The choice of the fermented papaya preparation was based on over 12 years of experimental and clinical data proving its effectiveness on redox and immune regulation. The aim of this study was to complete a 24-month investigation of the potential beneficial effect of this functional food on key age-related immune system parameters.

Methods: Study population: From a total of 106 subjects, we analyzed data collected from ninety-eight clinically stable, healthy community dwelling males and females aged 58 to 76 years. The investigation followed a double-blind methodology involving two groups, A and B. Group A received FPP® 4.5 grams, one sachet twice a day, coupled with a placebo capsule in the morning. Meanwhile, Group B was administered a papaya-flavored sachet twice a day, with an additional antioxidant mixture capsule in the morning, referred to as the AA group.  Morning blood samples were collected and tested for: Asymmetric dimethylarginine (ADMA), apoptosis of PBMCs and blood including Neutrophil-Lymphocyte Ratio (NLR) after 12 months, i.e. corresponding to 24 months of the 2-year study (Visit VI of the initial protocol). 

Results: As compared to the first preliminary published year of the study, this further 12-month study enabled a more comprehensive analysis with a significant increase of analyzed overweight (≥25 and ≤29.9 kg/m2) subjects (58 vs 31, P<0.05). On the 24-month mark, AA-group showed a significant increase of NLR (P<0.05 vs entry level and FPP group), whereas FPP-group maintained a stable value. Urinary 8-OHdG values maintained, as in the preliminary study, a wide dispersion of data but both treatments equally reduced its value in over 27BMI/r over 70y old subjects, which as taken separately, had significantly elevated values (p<0.05 vs younger subjects). ADMA and frequency of apoptotic cells values were beneficially reduced only by FPP supplementation throughout all 24 months of the study (P<0.05 vs baseline and vs AA supplementation). A significant correlation between NLR and Apoptosis of PBMCs appeared in FPP-treated subjects and this was more pronounced in subjects with >27BMI or over 70 years of age.

Conclusions: The novelty of the present work was the finding that FPP represents a substantial pharma-grade, non-GMO technological advancement over uncontrolled traditional plant extracts. This functional food affects oxi-inflammatory aging phenotype and NLR, a marker worth great attention for its preventive interventional potential in middle-age/elderly communities health care. 

Keywords: Fermented Papaya Preparation, NLR, ADMA, apoptosis, antioxidants, SARS-Cov19





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