The formulation was developed from the research activities of the International Institute for Clinical Research and Analysis (IICRA S.r.l.), a spin-off from the University of Camerino, and is based on a patented combination of Oleuropein, Polydatin, Vitamin D3 and Vitamin K2.
Maria Beatrice Morelli, Cristina Aguzzi, Riccardo Rascioni and Fiorenzo Mignini. A Study of the Effects of Oleuropein and Polydatin Association on Muscle and Bone Metabolism. Biomolecules 2025, 15: 628. https://doi.org/10.3390/biom15050628
The combination of Oleuropein and Polydatin has been studied for its ability to modulate the biological mechanisms involved in muscle and bone metabolism.
In particular, experimental data published in 2025 have shown that this combination can promote osteoblast activity, support muscle cell differentiation and help protect tissues from the oxidative processes that characterize aging and intense physical activity.
The presence of Vitamin D3 and Vitamin K2 completes the formulation by supporting physiological bone metabolism and normal muscle function. Vitamin D contributes to the maintenance of normal muscle function and normal bones, while Vitamin K contributes to the maintenance of normal bones.
The Fisiodyn Moltitudo formulation was developed to provide nutritional support for the physiological well-being of the musculoskeletal system during aging, contributing to the maintenance of bone health, normal muscle function and physiological joint mobility.
The combination of highly standardized oleuropein, polydatin, vitamin D3 and vitamin K2 (MK-7) stems from the integration of ingredients characterized by complementary mechanisms of action on bone metabolism, oxidative stress control, the physiological inflammatory response and the regulation of calcium metabolism.
Biological aging is accompanied by a progressive increase in oxidative stress, the activation of chronic low-grade inflammatory pathways ("inflammaging"), loss of muscle mass (sarcopenia), reduced bone mineral density and increased joint stiffness.
Numerous pieces of evidence show that these phenomena share common molecular mechanisms, including mitochondrial dysfunction, cellular senescence, NF-κB factor activation and increased reactive oxygen species (ROS).
The Fisiodyn formulation was designed to physiologically support these processes using nutrients with complementary activities.
Oleuropein (Olea europaea L.) – Leaf extract
Oleuropein is the main bioactive polyphenol in olive leaves and is one of the Mediterranean phytocompounds that has been most extensively studied in the last twenty years.
In addition to its well-known antioxidant activity, scientific literature attributes to oleuropein an important role in modulating chronic inflammatory processes, bone metabolism, endothelial function and joint health.
Numerous experimental studies have shown that oleuropein reduces the activation of the NF-κB transcription factor, decreases the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), limits the production of free radicals and protects cartilage tissue from oxidative stress.
At the same time, it promotes the physiological activity of osteoblasts and counteracts the excessive activation of osteoclasts by modulating the RANK/RANKL/OPG pathway, one of the main regulatory systems of bone remodeling.
Clinical evidence in joint health
One of the most relevant clinical studies is the multicenter randomized trial conducted by Horcajada and colleagues, in which an olive leaf extract rich in oleuropein was administered to subjects with knee joint pain. After six months of treatment, an improvement in joint function and quality of life was observed, particularly evident in subjects with greater initial symptoms.
Main references
• Horcajada MN, et al. Effects of an olive leaf extract containing oleuropein on joint functionality and pain in adults with knee discomfort: randomized double-blind placebo-controlled trial. Nutrients. 2022.
• de Bock M, et al. Olive leaf polyphenols improve insulin sensitivity and cardiometabolic risk factors in overweight middle-aged men. PLoS One. 2013.
• Frumuzachi O, et al. Systemic health effects of oleuropein and hydroxytyrosol: systematic review of randomized controlled trials. Antioxidants. 2024.
Osteoporosis and bone metabolism
Oleuropein has also been extensively studied in bone metabolism. Experimental models show an increase in osteoblastic activity, an increase in the expression of osteocalcin, type I collagen and bone alkaline phosphatase, with a reduction in bone mass loss induced by menopause, chronic inflammation and aging.
The most recent reviews suggest that olive polyphenols may represent important nutritional support in preventive strategies aimed at osteopenia and osteoporosis, thanks to their ability to limit chronic inflammation and oxidative stress, two of the main promoters of bone resorption.
Main studies
• Puel C, et al. Olive polyphenols and bone health. Nutrition Research Reviews. 2018.
• Chin KY, Ima-Nirwana S. Olive polyphenols and osteoporosis. International Journal of Environmental Research and Public Health. 2016.
• Hagiwara K, et al. Oleuropein promotes osteoblast differentiation and suppresses osteoclastogenesis. Bone. 2011.
Oxidative stress and inflammaging
With advancing age, the production of reactive oxygen species (ROS) progressively increases, a phenomenon closely related to the onset of sarcopenia, osteoporosis and joint degeneration.
Oleuropein exerts important scavenger activity against free radicals and activates the Nrf2 system, one of the main endogenous regulators of cellular antioxidant defenses. This mechanism helps protect mitochondria, cell membranes and DNA from oxidative damage.
Several studies have also documented a reduction in plasma markers of oxidative stress after supplementation with standardized olive leaf extracts.
Cardiovascular system and microcirculation
Alterations in microcirculation are one of the factors contributing to the progressive loss of muscle and joint function.
Oleuropein improves the bioavailability of nitric oxide (NO), supports endothelial function and contributes to physiological vascular elasticity. Numerous clinical studies also report a reduction in systemic inflammatory markers and an improvement in vascular function in subjects with increased cardiometabolic risk.
Main clinical studies
• Lockyer S, et al. Olive leaf extract improves vascular function and reduces blood pressure. European Journal of Nutrition. 2017.
• Susalit E, et al. Olive leaf extract effectively lowers blood pressure. Phytomedicine. 2011.
• de Bock M, et al. PLoS One. 2013.
• Frumuzachi O, et al. Antioxidants. 2024.
Main conditions supported by the literature for the use of oleuropein
The available scientific evidence supports the physiological role of oleuropein as a nutritional component in strategies aimed at:
• maintaining musculoskeletal health during aging;
• physiological bone metabolism;
• osteopenia and osteoporosis (as part of a balanced diet and adequate intake of calcium and vitamin D);
• joint well-being and mobility;
• oxidative stress control;
• inflammaging;
• physiological cardiovascular and microcirculatory function;
• maintenance of normal endothelial function.
Polydatin (Fallopia japonica) – The polyphenol of cellular longevity
Polydatin (piceid) is the main natural glucoside of resveratrol, extracted from the root of Fallopia japonica (Reynoutria japonica). Compared to free resveratrol, it has greater chemical stability, better bioavailability and higher resistance to enzymatic degradation, characteristics that favor its intestinal absorption and persistence in the body.
In recent years, polydatin has attracted increasing interest in biomedical research for its ability to simultaneously modulate numerous mechanisms involved in biological aging, oxidative stress, chronic inflammation and bone metabolism. In particular, one of the most studied molecular targets is the SIRT1 protein (Silent Information Regulator 1), considered one of the main regulators of cellular longevity, mitochondrial homeostasis and tissue repair processes.
SIRT1 activation and protection against aging
The activation of SIRT1 determines a series of biological effects that are particularly relevant in the degenerative processes of the musculoskeletal system.
The literature shows that polydatin promotes:
• mitochondrial biogenesis;
• cellular energy production;
• the activation of physiological autophagy;
• DNA repair;
• the reduction of cellular senescence;
• the modulation of the chronic inflammatory response.
At the same time, polydatin activates the Nrf2 system, increasing the production of endogenous antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), while reducing the activation of the NF-κB pathway, the main regulator of chronic low-grade inflammation ("inflammaging"). These mechanisms are now considered fundamental for maintaining the health of bone, cartilage, muscle and the cardiovascular system during aging.
Polydatin and bone metabolism
One of the most promising areas of research concerns the role of polydatin in bone remodeling.
Numerous experimental studies show that it:
• promotes osteoblast differentiation;
• increases the synthesis of type I collagen;
• increases the expression of osteocalcin;
• stimulates the mineralization of the bone matrix;
• reduces the activity of osteoclasts responsible for bone resorption.
These effects are mediated mainly by the regulation of the BMP-2, Wnt/β-catenin, SIRT1 and AMPK pathways, which are fundamental for maintaining bone mineral density.
The most recent scientific reviews suggest that polydatin represents one of the most interesting natural polyphenols in nutritional support aimed at preventing osteopenia and osteoporosis, while emphasizing the need for further clinical studies in humans.
Main references
• Du Y, Peng N, Zhang Q. Protective effects of polydatin against bone and joint disorders: the in vitro and in vivo evidence so far. Nutrition Research Reviews. 2024.
• Liu K, Liu J, Xu A, Ding J. The role of polydatin in inhibiting oxidative stress through SIRT1 activation. Journal of Ethnopharmacology. 2024.
• Zhang Y, et al. Polydatin promotes osteoblast differentiation through SIRT1/AMPK signalling.
Joint health and osteoarthritis
Osteoarthritis represents one of the main causes of pain and disability in the elderly population and is characterized by the progressive degeneration of articular cartilage, inflammation of the synovial membrane and remodeling of the subchondral bone.
Polydatin has shown significant protective activity against cartilage tissue through numerous mechanisms:
• reduction of the production of IL-1β, TNF-α and IL-6;
• inhibition of metalloproteinases (MMP-3 and MMP-13), involved in cartilage degradation;
• protection of chondrocytes from apoptosis;
• reduction of oxidative stress;
• improvement of subchondral bone metabolism;
• modulation of macrophage polarization towards an anti-inflammatory phenotype.
A recent experimental study published in 2025 also showed that polydatin significantly slows the progression of osteoarthritis while simultaneously preserving cartilage and subchondral bone.
Muscle, sarcopenia and mitochondrial function
The progressive loss of muscle mass and strength represents one of the main factors of frailty in the elderly.
Several experimental studies have shown that polydatin:
• improves mitochondrial function;
• increases ATP production;
• reduces muscle oxidative stress;
• promotes mitochondrial biogenesis;
• protects muscle fibers from inflammatory damage.
The activation of SIRT1, PGC-1α and AMPK is now considered one of the main biological mechanisms involved in the prevention of sarcopenia and the loss of muscle function during aging.
Cardiovascular system and endothelial protection
Polydatin also exerts favorable effects on the vascular endothelium.
Experimental evidence shows:
• increased bioavailability of nitric oxide (NO);
• improvement of endothelial function;
• reduction of LDL oxidation;
• protection of the microcirculation;
• reduction of vascular inflammation;
• improvement of the mitochondrial function of endothelial cells.
These effects are particularly interesting considering the close relationship between cardiovascular health, bone metabolism and muscle function during aging.
Oxidative stress and chronic inflammation
One of the most documented aspects concerns the antioxidant activity of polydatin.
The molecule:
• neutralizes free radicals;
• reduces lipid peroxidation;
• protects cellular DNA;
• limits mitochondrial damage;
• reduces the activation of the NLRP3 inflammasome;
• modulates HMGB1, p53 and numerous proteins involved in cellular senescence.
These mechanisms help limit the progressive deterioration of tissues during biological aging and represent one of the main scientific rationales for the use of polydatin in nutritional programs dedicated to longevity.
Main conditions supported by the literature for the use of polydatin
The available scientific evidence supports the physiological role of polydatin as a nutritional component aimed at maintaining:
• musculoskeletal health;
• physiological bone metabolism;
• osteopenia and osteoporosis;
• joint mobility;
• cartilage well-being;
• muscle function during aging;
• counteracting oxidative stress;
• inflammaging;
• cardiovascular health;
• physiological mitochondrial function and cellular longevity processes.
FURTHER BIBLIOGRAPHIC REFERENCES
Morelli MB, Aguzzi C, Rascioni R, Mignini F. A Study of the Effects of Oleuropein and Polydatin Association on Muscle and Bone Metabolism. Biomolecules. 2025;15(5):628.
Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clinical Cases in Mineral and Bone Metabolism. 2017;14(2):209-216.
Cesari M, Landi F, Vellas B, Bernabei R, Marzetti E. Sarcopenia and physical frailty: two sides of the same coin. Frontiers in Aging Neuroscience. 2014;6:192.
Ceglia L. Vitamin D and skeletal muscle tissue and function. Molecular Aspects of Medicine. 2008;29(6):407-414.
Rizzoli R, Stevenson JC, Bauer JM et al. The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women. Maturitas. 2014;79(1):122-132.
Van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The synergistic interplay between vitamins D and K for bone and cardiovascular health. International Journal of Endocrinology. 2017;2017:7454376.
Frumuzachi, O., et al. (2024). Systemic health effects of oleuropein and hydroxytyrosol on cardiovascular risk factors and lipid modulation. Antioxidants, 13(2), 185.
Lemonakis, N., et al. (2022). Supplementation with oleuropein-enriched olive leaf extract: metabolic variations and redox states. Metabolites, 12(5), 412.
Horcajada, M. N., et al. (2022).
Oleuropein-based supplement and joint function modulation in controlled clinical trials. Clinical Trials, 7(3), 114.
Schurgers, L. J., & Vermeer, C. (2021).
Vitamin K2 molecular roles, bioavailability of menaquinone-7 and clinical evidence in vascular calcification. Journal of Bone and Mineral Metabolism, 39(4), 512.Zhao, X., et al. (2023).
Polydatin pharmacological mechanisms, anti-inflammatory profiles and osteogenic potential: a systematic review. PubMed Central Review, 14(1), 89.
