Hyaluronic Acid

Hyaluronic acid (HA) is an important component of synovial fluid and normal cartilage and is thought by some to protect the articular cartilage and soft tissue surfaces of the knee by acting as a lubricant and imparting viscoelastic properties to the joint because of its high viscosity.
It’s a high-molecular weight glycosaminoglycan that consists of a repeating sequence of disaccharide units composed of N-acetyl glucosamine and glucuronic acid. It is produced by type B synoviocytes and synovial fibroblasts and is secreted into the joint, where it serves as a lubricant, shock absorber and chondroprotective milieu, to facilitate chondrocyte nutrition and to curb inflammation. The concentration of HA in the synovial fluid of patients with knee osteoarthritis is lower than that of normal synovial fluid. Intraarticular HA treatment has been proposed as a means of relieving symptoms, improving joint function, and potentially halting deterioration of the joint.

Osteoarthritis

Osteoarthritis (OA) is a chronic joint disease characterized by progressive destruction of joint cartilage and its associated structures (such as bone, synovial and fibrous joint capsules, and the periarticular musculature), producing significant pain and disability. There are two distinct forms of OA: primary (idiopathic) and secondary. Primary OA has no discernible trigger but may be associated with aging and/or lifestyle factors (e.g., jobs that involve repetitive tasks such as kneeling or squatting or participation in sports such as football or soccer). Secondary OA can be the result of various pathological conditions, such as joint injury, infection, or developmental or metabolic disorders. Advanced age and obesity are major risk factors for the development of OA, and with current population trends demonstrating significant increases in both, the prevalence of OA is expected to increase substantially in the coming years. Although several options are available for treatment of OA symptoms – simple analgesics, nonsteroidal anti-inflammatory drugs, intraarticular injection of glucocorticoids, and hyaluronic acid preparations – no medical intervention has been shown to halt disease progression or reverse joint damage in humans.

Bioactive Collagen Peptides Fortigel®

Bioactive collagen peptides are a combination of amino acids, with molecular weights from 3 to 10 kDa, that stimulate the synthesis of collagen in the extracellular matrix of cartilage and other tissues. In fact, bioactive collagen peptides Fortigel® are absorbed from the intestine in their high molecular form and distribute to hyaline cartilage, where they accumulate, and stimulate chondrocyte metabolism, increasing the biosynthesis of type II collagen and proteoglycans in the extracellular matrix. A study conducted on subjects with knee osteoarthritis has showed the dGEMRIC index (a technique to detect change in proteoglycan content in knee cartilage) increased in the medial and lateral tibial regions in subjects taking Fortigel®, but decreased in the placebo group. The effect of bioactive collagen peptides on pain from osteoarthritis was studied: patient taking Fortigel® experienced a statistically significant benefit in terms of pain reduction and functional improvement. In addition, 69% of patients had a ≥ 50% decrease in the consumption of analgesics. Bioactive collagen peptides are classified as a safe food by the European Food Safety Authority and by the Food and Drug Administration (FDA).

Rose-hip (Rosa canina)

A standardized rose-hip powder produced from the seeds and husks of fruit from a subtype of Rosa canina has been reported to inhibit leukocyte functions that cause cell injury in osteoarthritis.
Pain is the cardinal symptom of osteoarthritis and small intra-articular traumas do occur due to degeneration of the cartilage. Injuries of this kind are reflected in biochemical responses, some of which involve cytokines. Cytokines have proinflammatory effects that are manifested as episodes of pain, joint swelling, and redness. The standardized rose-hip powder inhibits the polymorphonuclear chemotaxis that is a step in the proinflammatory action of various cytokines. In a study, 94 patients (age > 35 years) with symptomatic knee and/or hip osteoarthritis were randomly allocated either to treatment with standardized encapsulated rose-hip powder or placebo. Pain declined as a result of active treatment after 3 weeks. In addition, an estimate of the consumption of rescue medication such as paracetamol showed a significant reduction in the rose-hip powder group.

Articular cartilage and Osteoarthritis

Articular cartilage, also known as hyaline cartilage, is a specialized, tough, flexible tissue with a low-friction coefficient and a smooth articulating surface that makes it ideally suitable for load distribution and absorbing the shock of movement. It is comprised of chondrocytes (about 2–10% of the volume of articular cartilage) and an extracellular matrix, which is maintained by the chondrocytes. The matrix of the articular cartilage consists of two components: the tissue fluid and the framework of structural macromolecules (such as type II collagen and proteoglycans) that give the tissue its form and stability. 60-80% of the matrix is water.
Osteoarthritis (OA) is a chronic joint disease characterized by progressive destruction of joint cartilage and its associated structures (such as bone, synovial and fibrous joint capsules, and the periarticular musculature), producing significant pain and disability. There are two distinct forms of OA: primary (idiopathic) and secondary. Primary OA has no discernible trigger but may be associated with aging and/or lifestyle factors (e.g., jobs that involve repetitive tasks such as kneeling or squatting or participation in sports such as football or soccer). Secondary OA can be the result of various pathological conditions, such as joint injury, infection, or developmental or metabolic disorders. Advanced age and obesity are major risk factors for the development of OA, and with current population trends demonstrating significant increases in both, the prevalence of OA is expected to increase substantially in the coming years. In recent years, various nutritional supplements have been investigated for the treatment of patients with OA and joint pain.

Bioactive collagen peptides Fortibone®

It has been shown that bioactive collagen peptides, a combination of amino acids, with molecular weights from 3 to 10 kDa, are rapidly absorbed from the gastrointestinal tract and may act as signaling molecules, thereby positively influencing anabolic processes. In fact, several studies have demonstrated the stimulatory effect of bioactive collagen peptides Fortibone® on the biosynthesis of bone extracellular matrix macromolecules. In a recent study, subjects with bone fractures of the upper or lower limbs or coccyx, treated with Fortibone®, clearly showed better bone healing than those who received the placebo. In addition, it appears that bone healing was accelerated with bioactive collagen peptides supplementation. The positive effects on healing of Fortibone® treatment are probably attributable to increased bone metabolism due to a direct impact on extracellular matrix turnover. These results suggest that bioactive collagen peptides Fortibone® can be used to improve fracture healing, and also to achieve faster healing. Bioactive collagen peptides are classified as a safe food by the European Food Safety Authority and by the Food and Drug Administration (FDA).

Bone Fractures

Bone, a calcified tissue composed of 60% inorganic component (hydroxyapatite), 10% water and 30% organic component (especially type I collagen and proteoglycans), has three functions: providing mechanical support for locomotion, protecting vital organs, and regulating mineral homeostasis. A lifelong execution of these functions depends on a healthy skeleton, which is maintained by constant bone remodeling in which old bone is removed by the bone-resorbing cell, osteoclasts, and then replaced by new bone formed by the bone-forming cell, osteoblasts. However solid and robust, bones can break (fracture) in response to the application of an external force that exceeds their resistance. Fracture is the partial or complete rupture of a bone. A fracture can occur due to direct (for example, a fall) or indirect (e.g. fracture of the leg of a skier or of a footballer who enters a twist due to the foot blocked by the boot or the ground). Sometimes, the fractures appear following minimal traumatism: this is what occurs for example when there is a severe form of osteoporosis, a condition that reduces the density of the bone and alters its architecture, making it less resistant and more prone fractures, which typically occur in the spine and femur. The complete and undisturbed healing of bone fractures is a key priority for surgeons and patients, so intensive efforts are made to improve bone healing with a variety of approaches. Oral therapies with collagen peptides are a relatively new therapeutic approach.

Tendons and ligaments act as essential connecting elements that transmit, distribute and modulate stresses that muscles exert on the skeletal system while in motion. Their structures are composed of extracellular matrix collagens, proteoglycans and elastic fibres, easily vulnerable when exposed to traumatic or microtraumatic injuries, especially when the body lacks certain micronutrients crucial to proper functioning. TENDOFORTE® (Bioactive Collagen Peptides®) has a stimulatory impact on the synthesis of extracellular matrix in tendon and ligament fibroblasts and a down-regulating effect on degradation processes. Oral intake of TENDOFORTE® has been shown to relieve joint- and tendon-related pain and improve resistance to mechanical stress, thereby reducing risk to injury; recovery times from injury are also reduced. In a study involving 20 subjects with chronic Achilles tendinopathy, it was observed that the prolonged administration of TENDOFORTE®, in combination with an appropriate rehabilitation program, promotes an improvement in symptoms related to chronic tendinopathies.

An analysis of the international literature has shown that the contribution of certain microelements is essential to prevent, mitigate, treat tendon damage caused by muscle activity:

• Methilsulfonilmethane (MSM): analgesic, anti-inflammatory and antioxidant effects.
• Glucosamine and chondroitin sulphate: increase collagen synthesis, ameliorate mechanical properties, organization of collagen bundles, and resistance to fatigue.
• Vitamin C: stimulates hydroxyproline synthesis of procollagen, as well as an anti-inflammatory and antioxidant effect.
• Biotin: contribute to normal functioning of the nervous system and normal macronutrient metabolism (glucides, lipids ad protides).

The scientific literature has shown that these elements, due to their marked synergistic activity, are particularly effective in maintaining the functionality of tendons and ligaments, in particular in subjects with nutritional deficiencies or under physical effort.

Tendons and ligaments

Tendons and ligaments are composed of extracellular matrix collagens, proteoglycans and elastic fibres and differ in their anatomical location. Ligaments attach bone to bone, while tendons transfer the tensile loads from muscle to bone so as to enable joint motion and stabilization. They are structures that are easily vulnerable to traumatic or microtraumatic insults, in particular when the organism is lacking in the nutritional microelements essential for the correct functioning and conservation of the tendon itself, as in the case of functional overload in sports which it leads, together with a strong stress on the joints and tendons, to rapid exhaustion of the micronutrients necessary for the well-being of the tendon itself, with a consequent increase in the probability of tendinopathy.Tendinopathies represent a clinical problem, characterized by pain, swelling and limited function, which affects both professional and recreational athletes and people involved in repetitive work, as well as elderly subjects.Tendons and ligaments Tendons and ligaments are composed of extracellular matrix collagens, proteoglycans and elastic fibres and differ in their anatomical location. Ligaments attach bone to bone, while tendons transfer the tensile loads from muscle to bone so as to enable joint motion and stabilization. They are structures that are easily vulnerable to traumatic or microtraumatic insults, in particular when the organism is lacking in the nutritional microelements essential for the correct functioning and conservation of the tendon itself, as in the case of functional overload in sports which it leads, together with a strong stress on the joints and tendons, to rapid exhaustion of the micronutrients necessary for the well-being of the tendon itself, with a consequent increase in the probability of tendinopathy. Tendinopathies represent a clinical problem, characterized by pain, swelling and limited function, which affects both professional and recreational athletes and people involved in repetitive work, as well as elderly subjects.

Docosahexaenoic (DHA)

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that falls into the larger category of polyunsaturated fatty acids. Many chronic conditions are associated with excessive intake of dietary saturated fatty acids (including obesity, insulin resistance, coronary heart disease, and some form of cancer). Clinical assessment of dietary supplementation of omega-3 polyunsaturated fatty acids, including DHA, indicate their beneficial impact on human diseases, such as peripheral neuropathy, in which inflammation is suspected as a key component of the pathogenesis. DHA has a positive effect on membrane fluidity and permeability, carrier-mediated transport of nutrients in and out of the cell, enzymatic activities and cell-to-cell communication. Recent studies have revealed that, during the course of acute inflammation, omega-3 polyunsaturated fatty acids-derived mediators, including DHA, with potent anti-inflammatory properties are produced (resolvins).

Alpha lipoic acid (ALA)

Of all the antioxidant nutrients, α-lipoic acid (ALA) seems to be the strongest for its unique ability to act as an antioxidant in both lipid and aqueous phases of the cell. Dietary sources include red meat, organ meats, spinach, broccoli, potatoes, yams, carrots, beets, and yeast. Neuropathy is induced oxidative stress-associated inflammation; ALA is well known for its antioxidant properties in cytokine-induced inflammation. In addition, ALA can regenerate endogenous antioxidants, such as vitamin E, vitamin C, and glutathione, and prevent oxidative damage. Endogenous ALA is also a coenzyme involved in carbohydrate metabolism, and in the mitochondrial citric acid cycle which produces adenosine triphosphate.

Formulation DHA + ALA

Some results obtained with a formulation ALA plus DHA demonstrate the inventive property of this combination, since the compounds have different chemical structures and act through different modes of action but which, when acting together, interact at the cellular level to elicit a therapeutically meaningful response almost immediately. In fact, the oral administration of ALA in combination with DHA brought about a greater effect than the sum of either component alone, indicating a synergic interaction in antagonizing the inflammatory effect. The combination of DHA and ALA represent an approach for sustaining the subjects with inflammations in the nervous system and therefore with neuropathies, such as canicolar syndromes of the hand, and lumbar and cervical syndromes.

Peripheral Neuropathies

Peripheral nerves are subject to the same types of problems as other tissues, inflammation, toxicity, swelling, leading to neuropathies. However, there are some differences, due to their structural uniqueness. The nerve fibers exist as units of motor neurons with long axons that innervate muscle fibers. They are grouped by the perineural sheath, a connective tissue wrapping. Individual nerve fibers contain the nerve axon along with its Schwann cells and protective myelin sheath coating. Regulation of the nerve microenvironment is accomplished by three barriers, the perineural barrier, the blood-nerve barrier, and the nerve-cerebrospinal fluid barrier. When these barriers are penetrated, inflammatory cells can infiltrate, causing neuropathies with inflammation, pain and atrophy. There is no single satisfactory treatment for most of the neuropathies, and many neuropathies have no known cause. A number of prescription drugs are used, but all have side effects, and none can actually correct the underlying nerve defect that causes the pain. Nutrients may offer an alternative for people who want to avoid the side effects of prescription drugs.

Menaquinone 7 (Vitamin K2)

Menaquinone 7 is a member of the Vitamin K2 family. Major source of Vitamin K2 are dairy products such as cheese and the traditional Japanese food natto (fermented soybeans). Vitamin K is required for the activation of glutamate into γ-carboxyglutamate (Gla) residues in so-called Gla-proteins, including osteocalcin synthesised in the bone. Active osteocalcin (cOC) is able to attract Calcium ions and incorporate them in hydroxyapatite crystals that form bone matrix. At a systemic level, concentrations of plasma cOC and its inactive form (ucOC) reflect the functional state of this protein in the bone matrix and have been shown to be a valid index to describe bone health: increased levels of ucOC were found in post-menopausal woman with increased bone loss, osteoporosis and increased fracture risk. Menaquinone 7 (MK-7) performs several functions, all related to its recognised effect on activation of certain Gla-proteins. MK-7 intake significantly improved Vitamin K status and decreased the age-related decline in bone mineral density (BMD) at the lumbar spine and femoral neck.
Then, improvement of Vitamin K status as measured by increased activation of OC is readily achievable by dietary supplementation with Vitamin K. Consistently, the European Food Safety Authorities (EFSA) accepted the health claim on Vitamin K’s role in maintenance of normal bone. So, postmenopausal women may benefit from taking MK-7 supplements to prevent the age-related bone loss.

Osteoporosis

Osteoporosis is a systemic skeletal condition that involves a reduction in bone mass and deterioration of the bone structure, making it more fragile with an increased risk of fractures. Postmenopausal women experience accelerated bone loss, which leads to osteoporosis and increased risk of development of fractures in the spine (vertebral crush fractures), forearm (Colles’ fractures) and hip. Osteoporotic fractures of the spine and forearm are associated with significant morbidity, but the most serious consequences of bone loss arise in patients with hip fracture, which is associated with a significant increase in mortality (15–20%), particularly in the elderly. Nutritional approaches to the prevention of osteoporosis are currently generating considerable interest, in particular regarding the recently found correlation between the severity of osteoporosis and dietary habits. Long-term Vitamin K inadequacy has been indicated as an independent but modifiable risk factor for the development of age-related diseases, including osteoporosis and cardiovascular disease.