Editorial information in collaboration with Esserre Pharma


Pre-clinical and clinical evidence has clearly shown that nutrition plays a decisive role in helping the immune system to function properly and that specific antioxidants and nutrients can help manage the feeling of lack of energy, prolonged tiredness, and physical and mental fatigue. Fatigue is experienced by 38% of adults in the general population, and can develop as a result of stressful events, nutritional deficiencies, inflammation, changes in the immune system, and infectious diseases. If the cause is not addressed specifically and promptly, this can lead to chronic fatigue, which is a real condition (myalgic encephalomyelitis).

To immediately reduce tiredness and fatigue, Esserre Pharma has formulated IMPROVE® Response, a food supplement that combines the antioxidant and anti-inflammatory properties of Mediterranean pomegranate extract, PunicaPLUS®, with B vitamins and vitamin C. PunicaPLUS®, standardized in polyphenol content, is obtained from the peel of pomegranates grown in a controlled supply chain in the Mediterranean basin.

The immuno-nutritional properties of pomegranate were also discussed at a recent symposium dedicated to Mediterranean nutraceuticals that was held as part of the recent congress of the Italian Nutraceutical Society in Bologna. Its antioxidant and anti-inflammatory activities are attributed to the polyphenolic compounds punicalagin A and B, and ellagic acid and its derivatives. Several studies have shown that the polyphenolic phytocomplex present in the peel of this fruit can have superior antioxidant activity compared to the individually purified polyphenols. In addition, pomegranate extract has renowned antibacterial, antiviral, anti-inflammatory, and possible immunomodulatory action. In particular, it has been shown that the protective mechanisms induced by ellagic acid are due to the reduction of nitric oxide, IL-1β, IL-6, and TNF-α.

To complete the synergy in managing fatigue, IMPROVE® Response contains vitamin B-Complex and vitamin C, which further contribute to the reduction of fatigue, support energy metabolism and immune system function, and contribute to protecting cells from oxidative stress.

The effectiveness of IMPROVE® Response in reducing fatigue in healthy subjects who have a prolonged state of fatigue has shown excellent results. The product is available in 1.6 g stick packs and the recommended dosage is 1 stick per day in 150 ml of water, which corresponds to the optimal dosage of pomegranate extract: 500 mg/day per day (100 mg of polyphenols per stick).

The nutraceutical is ideal in its anti-fatigue effectiveness together with a daily diet that is rich in antioxidants from fresh seasonal fruit and vegetables, which should form the basis for complete nutrition. Pomegranate, eaten as a fruit with its grains or as a juice, can enrich the daily diet of those who use IMPROVE® Response because its polymeric compounds are hydrolyzed in the intestine to ellagic acid which is metabolized by gut microbiota into urolithins, which have anti-inflammatory action.

In vitro and in vivo antioxidant activities of three major polyphenolic compounds in pomegranate peel: Ellagic acid, punicalin, and punicalagin. Journal of Integrative Agriculture 2017, 16(8): 1808–1818.
Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC Complementary and Alternative Medicine (2017) 17:47.
Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of interleukin-10 via an antioxidant mechanism. International Immunopharmacology 19 (2014) 290–299.
Evaluación de la actividad inmunomoduladora del polvo seco de Punica granatum Linn en un modelo experimental de inmunosupresión. Revista Cubana de Medicina Militar. 2019;48(2):177-186.
Immunomodulatory Role of Urolithin A on Metabolic Diseases. Biomedicines 2021, 9, 192.