4. Discussion
fatigue
INFLAMMATION, SECONDARY, TYPE 2 DIABETES
In this study, a combination of a chemically characterized pomegranate extract (rich in dietary polyphenols) and hydro-soluble vitamins (i.e., B complex and C) used as a food supplement was studied for its efficacy in the improvement in prolonged fatigue in a monocentric, randomized, double-blind, placebo-controlled clinical trial.RP-UHPLC analysis coupled with a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer showed the presence of 59 compounds in the pomegranate extract. The results support previous reports on the phytochemical composition of pomegranate extracts, although no study to date has determined the metabolic profile of these extracts in such detail [According to European legislation, food supplements could be provided for the healthy population as they may exert nutritional or physiological effects but cannot exert therapeutic effects [As a secondary outcome, a questionnaire on the quality of life, SF-12, was used. The results show a slight, non-significant tendency toward an increase in the quality of life, with SF-12 values increasing from 30.5 (t0) to 32 (t3) for the food supplement group. For the placebo group, the recorded SF-12 values were constant (SF-12 values ranging from 27.6 at t0 to 27.7 at t3).These results, taken together, are consistent with previous findings on pomegranate extract and hydro-soluble vitamins. Swamy et al. [Regarding the other secondary outcomes (measured at t0 and t2), the intake of the food supplement did not show a significant effect on the biochemical markers between the beginning and the end of the clinical trial, as they remained quite constant and within normal ranges for both food supplement and placebo groups.In particular, as far as IL-6 is concerned, the recruited subjects had IL-6 blood values typical of healthy subjects as defined by a recent meta-analysis, including 57 published studies with 3196 IL-6 values recorded in the blood of healthy donors, which reported that the average IL-6 blood levels range from 4.631 to 5.740 pg/mL in the majority of healthy individuals. Literature data reported that pomegranate polyphenols possess high biological activity during pathological inflammation. In fact, following an intake of pomegranate juice or extract, several clinical trials have shown a decrease in IL-6 blood levels in patients suffering from type 2 diabetes [This study shows strengths and limitations. The main strengths are that the efficacy of the food supplement was determined in a clinical trial with a robust design, suggesting that it is a safe and effective treatment for a large part of the population with mild to moderate prolonged fatigue. The main limitations are that it was not possible to show an improvement in the quality of life after the supplementation, probably due to the way the sample number calculation was conducted on the primary outcome, namely the FSS questionnaire, the number of subjects is insufficient to provide a statistically significant conclusion for this increase in SF-12, and the mechanism through which the food supplement exerts its effect is still largely unknown.In conclusion, this study shows that a food supplement based on the combination of a chemically characterized pomegranate extract, B vitamins, and vitamin C, supplemented for two months of intake in healthy consumers, reduces prolonged fatigue. The mechanism of action is yet to be elucidated, but considering the high content of ellagitannins in this pomegranate extract that are able to reshape the gut microbiota by increasing eubiotic bacteria (