Actiful is a blend of Citrus sinensis (sweet orange) and Punica granatum (pomegranate) extracts - plants with high levels of bioactive polyphenolic components, mainly flavonoids.
The current paper is a new reading of data from a previously published randomised double blinded crossover study, performed by researchers at Maastricht University, Netherlands, with one researcher from Bioactor.
The new analysis suggests the potential of Actiful as a dietary modulator against advanced glycation end-products (AGEs) - a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease.
To be precise, after a 4-week period of supplementation in healthy elderly subjects, there was a 9.8% (p = 0.042) drop in plasma levels of methylglyoxal (MGO) - a toxic compound that leads to the production of advanced glycation end products (AGEs).
The authors say these new clinical results highlight the ingredient's potential to mitigate age related diseases like diabetes, vascular dysfunction and neurodegeneration.
This is the first human intervention study to investigate the effects of a combination of sweet orange extract and pomegranate fruit concentrate on reactive α-DCs.
The authors state: "If supported by further research, these findings have the potential to influence the creation of specialized dietary supplements or nutraceuticals targeting MGO-related health concerns.
"Additionally, this study’s insights hint at the vast potential of phytochemicals in various fruits and plants that might offer therapeutic properties against MGO. Through these revelations, we are establishing a foundation for future research, aiming for innovative solutions to challenges posed by elevated MGO levels."
Several experimental in vitro studies have found that citrus and pomegranate polyphenols can scavenge reactive α-dicarbonyls (α-DCs) and prevent the formation of AGEs.
α-DCs are known to contribute to the formation of advanced glycation end-products (AGEs).
Hesperidin, the primary flavonoid glycoside in sweet orange extract, has MGO and GO trapping ability while pomegranate extract’s principal polyphenolic compounds, punicalagin and ellagic acid, exhibit potent antioxidant activity.
Some in vitro experimental studies report that ellagic acid and urolithin A, a gut microbiota metabolite of ellagitannins and ellagic acid, inhibit non-enzymatic glycation by scavenging MGO.
The authors of the current study say despite experimental evidence, controlled human studies on the effects of orange and pomegranate actives on α-DCs levels are lacking.
The original RCT, conducted by researchers at Maastritch University and Bioactor, was published last August and concluded that four weeks of daily supplementation with Actiful significantly improves handgrip strength and self-evaluated measures of psychological function in healthy older adults.
The current study focuses on the evaluation of additional biomarkers and the effect of supplementation in reducing the concentrations of reactive α-DCs compounds (specifically methylglyoxal, glyoxal, and 3-deoxyglucosone) in blood samples.
Thirty-six healthy elderly subjects were recruited for this double-blind, randomized crossover clinical trial. They received either 700 mg of Actiful in capsules, or a
placebo for four weeks, with a 4-week washout period in between.
Blood samples were collected during the test day to measure α-Dicarbonyls in plasma. This was achieved via ultra-performance liquid chromatography tandem
The observed reduction in methylglyoxal was around 9.8%, which the authors say was significant and could be of clinical relevance in preventing or managing previously mentioned age-related conditions related to AGEs formation, like cardiovascular related diseases, diabetes and neurodegeneration.
The firm asserts the ingredient has a dual mode of action. Firstly, through increasing synthesis of nitric oxide. Secondly, it says the ingredient can improve production of ATP (Adenosine triphosphate), an organic compound that provides energy to drive and support many processes in living cells.
The authors say these results signal the need for further research: "Based on these initial findings, several recommendations and prospective avenues emerge. It is essential to substantiate these preliminary discoveries with broader studies, involving a more diverse group of participants. Investigating the optimal doses of the combined extracts is crucial for refining the MGO scavenging effect. Moreover, determining the specific molecular pathways through which these compounds act will enhance our understanding and may lead to the development of even more effective interventions."
Source: International Journal of Molecular Sciences
"A Citrus and Pomegranate Complex Reduces Methylglyoxal in Healthy Elderly Subjects: Secondary Analysis of a Double-Blind Randomized Cross-Over Clinical Trial"
Bednarska, K.; Fecka, I.; Scheijen, J.L.J.M.; Ahles, S.; Vangrieken, P.; Schalkwijk, C.G.