Abstract
In recent years a number of studies have reported the significant relationship between metabolic syndrome and neurodegenerative disease. There is accumulating evidence that the interplay of combined genetic and environmental risk factors (from diet to life style to pollutants) to intrinsic age-related oxi-inflammatory changes may be advocated for to explain the pandemic of neurodegenerative diseases. In recent years a specific Fermented Papaya Preparation (FPP) has been shown to significantly affect a number of redox signalling abnormalities in a variety of chronic diseases and as well in aging mechanisms either on experimental and on clinical ground. The aim of the present study was to evaluate FPP use in impending metabolic disease patients with potentially neurodegenerative disease clustered risk factors. The study population consisted of 90 patients aged 45–65 years old, with impending metabolic syndrome and previously selected as to be ApoE4 genotype negative. By applying a RCT, double-blind method, one group received FPP 4.5 g twice a day (the most common dosage utilized in prior clinical studies) while the other received an oral antioxidant cocktail (trans-resveratrol, selenium, vitamin E, vitamin C). Then, after 21 month treatment period, a selected heavy metal chelator was added at the dosage of 3 g/nocte for the final 3 months study treatment. The parameters tested were: routine tests oxidized LDL-cholesterol, anti-oxidised LDL, Cyclophilin-A (CyPA), plasminogen activator inhibitor-1 and CyPA gene expression. From this study it would appear that FPP, unlike the control antioxidant, significantly decreased oxidized-LDL and near normalizing the anti-Ox-LDL/Ox-LDL ratio (p<0.001) although unaffecting the lipid profile per sè. Moreover, only FPP decreased cyclophilin-A plasma level and plasminogen activator-inhibitor (p<0.01) together with downregulating cyclophilin-A gene expression (p<0.01). Insulin resistance was only mildly improved. Heavy metals gut clearance proved to be effectively enhanced by the chelator (p<0.01) and this was not affected by any of the nutraceuticals, nor it added any further benefit to the biological action of FPP.
Highlights
Starting in the early 90’ gold standard electron spin resonance studies had shown that a functional food consisting of fermented papaya (FPP, ORI, Oxidative Stress laboratory, Gifu, Japan) exhibited a powerful anti-oxidative activity on in vitro cerebral cells [1] as well on in vivo epilepsy experimental model, where the epileptogenic monoamine neural release was consistently reduced [2]
Recent studies using transgenic mice have shown the importance of proinflammatory Cyclophilin A (CypA)-metalloproteinase-9 in blood-brain-barrier integrity [9] while other have proved that a specific inhibitor of CyPA could reduce neuroinflammation, improve motor neurons activity and prolong survival in a mouse model of amyotrophic lateral sclerosis [10]
Whereas the group treated with antioxidant cocktail did not show any statistically significant difference in the oxidised lipid asset, patients treated with Fermented Papaya Preparation (FPP) showed a significant improvement of these parameters (Figure 2)
Summary
Starting in the early 90’ gold standard electron spin resonance studies had shown that a functional food consisting of fermented papaya (FPP, ORI, Oxidative Stress laboratory, Gifu, Japan) exhibited a powerful anti-oxidative activity on in vitro cerebral cells [1] as well on in vivo epilepsy experimental model, where the epileptogenic monoamine neural release was consistently reduced [2]. The potential neuroprotective effects of FPP are at the moment the target of a clinical study on Parkinson’s disease patients by the neurology group of Nordera. This group has reported some preliminary promising results such as a reduction of motor scores of the Unified Parkinson Disease Rating Scale, improvement of Activity of Daily Living performance and of redox biochemistry Personal communication at Oxidative Stress in Health and Prevention, September 24, 2014 http://www.centrostressossidativo.it/ video-congresso-stress-ossidativo/) It has been recently shown that FPP could dramatically decrease the oxidative stress parameters in established Alzheimer Disease (AD) patients [12]
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