Collagen I, II, III
Collagen is the most abundant protein in the human body and in mammals. It forms fibres in the extracellular matrix, giving shape and mechanical properties to tissues. There are 28 types of collagen in our body, of which the first 3 are the most abundant. Type I collagen is mainly present in tendons, skin, blood vessel walls, cornea, the organic part of bones and teeth, around muscle fibres and plays an important role in tissue repair. Type II collagen accounts for 50% of the proteins in our cartilage and is present in the eye (the vitreous humor). Type III collagen is also present in the walls of blood vessels, skin, intestines and uterus. It is less robust than type I collagen, but the two are often combined in these tissues.
The effectiveness of collagen peptides has been highlighted in cases of osteoarthritis. The scores WOMAC1 and VAS2 have decreased, demonstrating a reduction in pain, joint stiffness and improved motor skills. This leads to a better quality of life for the patients in their daily activities.3–5
Type II collagen peptides help reduce rheumatoid arthritis, an inflammatory disease in which the immune system attacks the joints, in particular because of the presence of collagen. When native type II collagen is taken orally, the immune cells become accustomed to it and the presence of collagen in the body become normal again (oral tolerance). In a randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. 6,7
For people who occasionally experience pain during sports or daily mobility, collagen peptides improve the extension capacity of the joint (e.g. knee), reduce pain and increase exercise time before discomfort.8 The consumption of collagen peptides also strengthens the stability of the joints and reduces the risk of repeated injuries. In sports people, performance is also improved. 9
The benefits of collagen hydrolysates are also found in cases of osteoporosis, decreasing the presence of bone decomposition markers and increasing mineral density, as well as bone regeneration markers.10–12
Lysine and threonine are essential amino acids, which means that our body cannot produce them and therefore we must provide them through our nutrition.
Lysine increases the absorption of calcium in the intestines and limits its evacuation through the urine, which helps to maintain healthy bones. It also promotes healthy blood vessels and smooth muscles and limits calcium deposits in the vessels by helping the calcium to move from the vessels to the bones.13,14
In addition, lysine is one of the amino acids necessary for the synthesis and then for the proper function and structure of collagen because it acquires numerous enzymatic modifications (post-translational modifications) and in particular those allowing the links in and between collagen chains.15 Lysine also inhibits MPPs (matrix metalloproteases), the enzymes responsible for collagen degradation.16
These properties make lysine a valuable ally in the healing of wounds, for example on the skin. For bone healing, lysine also accelerates healing by 2 weeks: it will activate the osteoblasts that ensure bone formation, increase calcium and collagen content, promote vascularisation and stimulate the secretion of growth factors and insulin (entry of glucose into cells).17,18
Threonine is also an essential amino acid brought by nutrition. It is very important for the good structure of our tissues, as it is the precursor of glycine, the main amino acid of collagen. Moreover, threonine incorporated in collagen plays an important role in the stability of collagen and the links between chains. Threonine is also present in elastin fibres. 19,20
Find out more about those amino acids
Glucosamine and chondroitin Sulphates
Glucosamine is a monosaccharide naturally present in our body. It is the precursor of several glycosaminoglycans such as hyaluronic acid, chondroitin or keratan sulphate, which make up aggrecans, very important constituents of the extracellular matrix. Chondroitin is the most abundant of those glycosaminoglycans in our cartilage. It enables water to be retained in the tissue and therefore maintains its osmotic pressure, elasticity and flexibility.
The benefits of taking glucosamine and chondroitin sulphates for osteoarthritis have been studied and debated for a long time because of the irregularity of the results and a sometimes high placebo effect. Nevertheless, most groups now agree on the usefulness of these supplements and their safety, as they are often better tolerated than some anti-inflammatory drugs.21 The GAIT study22 in 2006 showed in 1583 patients that taking glucosamine and chondroitin combined made it possible to reduce daily pain (OARSI-OMERACT score)23 of people suffering from moderate or severe osteoarthritis. Other studies have pointed out that the combination of glucosamine and chondroitin can reduce pain in the same way as taking a narcotic analgesic (2x 50mg of Tramadol)24 or a COX2 inhibiting non-steroidal anti-inflammatory drug (Celecoxib)25, and increase mobility of the joint (temporomandibular or knee). This combination was associated with an improvement in Lequesne score26, showing better functioning of the disabling joint, and in the WOMAC score1, highlighting a decrease in pain in daily life. It could also reduce swelling, effusion and stiffness of the joint when the osteoarthritis is not too advanced.27–31 By limiting the progression of the disease and its symptoms over the long term, taking chondroitin and glucosamine reduces the risk of total joint replacement.32 Symptom improvement can be even more effective when glucosamine and chondroitin are combined with a source of flavonoids,31 like rosehip.
Find out more about chondroitin and glucosamine
Hyaluronic acid (as sodium salt: sodium hyaluronate)
Hyaluronic acid is one of the major components in the extracellular matrix. It combines with chondroitin and keratin sulphates and intermingles with collagen fibres. It has excellent viscoelasticity and high water-retention capacities, allowing it to lubricate, absorb shocks, regulate the water balance and stabilise the structure of the joint.33
It also protects against inflammation and oxidative stress. When taken, it reduces the production of nitric oxide and free radicals and increases the synthesis of antioxidants, thus reducing oxidative stress.33,34 It also mitigates the production of pro-inflammatory mediators, such as cytokines, bradykinin and prostaglandin, to limit over-inflammation.33 In addition, by interacting with nerve endings (which become less sensitive and therefore transmit less pain), hyaluronic acid also has analgesic properties.35
The benefits of hyaluronic acid have been observed on the joints in general. It increases joint mobility and function, reduces stiffness and pain. In addition, it increases the endogenous synthesis of proteoglycans, collagen and hyaluronic acid by synoviocytes and chondrocytes (cells of the joint), increasing cartilage regeneration. It also inhibits osteoclasts, which resorb subchondral bone and weaken the joint. It will also increase the density and vitality of chondrocytes, the cartilage cells that produce the molecules necessary for healthy, functional cartilage. The proliferation of fibroblasts and keratinocytes, as well as the synthesis of collagen fibres will also be increased. The properties of hyaluronic acid are therefore very important for healing. In the case of osteoarthritis, the levels of inflammation and oxidation are high, increasing cell death and damaging cartilage, bone and synovial fluid. Taking hyaluronic acid restores the properties of the synovial fluid and the metabolism of the joint cells. Several studies have pointed out that increasing the amount of hyaluronic acid in the joint leads to improved joint function, and reduced pain and stiffness. This is reflected in a reduction in VAS, WOMAC and Lequesne scores, highlighting an improvement and slowing of disease progression.33,37–39
Find out more about hyaluronic acid
Thanks to its sulphur composition, MSM is an agent against inflammation and oxidative stress. It will, for example, desensitize the immune system, reduce inflammatory cytokines and inhibit vasodilatation in chronic inflammation. It has a strong antioxidant power, notably by stimulating reducing enzymes and inhibiting certain cellular processes involved in the generation of free radicals.40
Thanks to its anti-inflammatory action, in particular through the suppression of inflammatory cytokines (TNFα, IL-1β), MSM can protect the cartilage and synovial fluid, thus improving the condition of the joint. It can also reduce pain after sport.40,41
Several clinical studies on osteoarthritis have shown that taking MSM reduces pain, stiffness and swelling in the joint, leading to improved physical function and daily performance. This is reflected in improved VAS (Continuous Pain Scale), WOMAC (joint function and pain), SF36 (quality of life) and Lequesne Index (joint function) scores, as well as a possible reduction in the use of anti-inflammatory drugs. Its anti-inflammatory and analgesic properties therefore make it a valuable ally in improving the symptoms of osteoarthritis and the quality of daily life.40,42–46
Taking MSM is also beneficial in arthritis because it reduces inflammation by reducing the expression of cytokines, certain inflammatory cell processes, as well as the amount of other markers such as anti-cyclic citrullinated peptide 2 (anti-CCP2), C-reactive protein (CRP) and rheumatoid factor (RF).40,47
These effects seem to be potentiated by an association with collagen or chondroitin-glucosamine.
Find out more about MSM
Rosehip has very powerful antioxidant powers, thanks to a high concentration of flavonoids, and contains more vitamin C than citrus fruits. It also has a high concentration of folate, vitamins A, B3, D and E, carotenoids, beta sitosterol, malic acid, tannins, magnesium, zinc, copper, as well as specific galactolipids and fatty acids such as linoleic acid, making it a long-appreciated health asset.36
The strong antioxidant properties of rosehip, thanks to its high content of flavonoids and phenolic compounds, protect against oxidative stress and ensure good communication and adhesion between cells. By increasing the activity of antioxidant enzymes (such as superoxide dismutase and catalase) rosehip reduces the concentrations of free radicals (ROS) and nitrogen oxides (NO) which can damage tissues. Rosehip extracts also have strong anti-inflammatory properties. Thanks to their fatty acid content, they inhibit the COX 1 and 2 enzymes as well as the metabolism of arachidonic acid, which otherwise induce numerous inflammatory mediators. Its galactolipids also block the synthesis of cytokines, chemokines, inflammatory prostaglandins by immune cells, limit the migration (chemotaxis) of lymphocytes in the blood, and reduce the blood concentration of inflammatory C-reactive proteins (CRP). Some of these components can furthermore moderate NFκB, whose overactivation induces inflammation, immune deregulation and tissue destruction.36,48,49
Rosehip extracts, especially its galactolipids, have a protective effect on cartilage and chondrocytes. They reduce the expression of genes linked to inflammation (cytokines, NO, PGE2, chemokines, etc.), as well as catabolic genes that degrade the extracellular matrix, particularly those of collagen-cleaving MMPs and aggregases.36,50,51 Rosehip may also limit inflammation of the synovial fluid, which may be associated with greater risk of osteoarthritis.52
Several clinical studies (placebo/blind double blind) have shown that taking rosehip extracts for at least 3 months is useful for osteoarthritis. Indeed, it helps to reduce pain and stiffness in the joint, limiting the dose of anti-inflammatory drugs required. It also leads to an increase in physical function (WOMAC score)1, which underlines a decrease in the severity of the disease.48,53,54 Rosehip is also effective against chronic back pain. Its pain-relieving properties are even more appealing because, unlike non-steroidal anti-inflammatory drugs (NSAIDs), rosehip does not influence coagulation and has no negative side effects such as ulcers.36
In the case of rheumatoid arthritis, an autoimmune disease in which our immune system attacks our joints, tissue damage is linked to a large amount of free radicals and nitrogen oxides. The strong antioxidant powers of rosehip limit their production, protecting cells from DNA and mitochondrial damage and limiting cell death.36
At the bone level, the presence of a small amount of free radicals can be beneficial because it signals the presence of calcified tissue to be disintegrated or a wound to be healed. However, too much oxidative stress can be linked to an increase in the activity of osteoclasts (bone resorption) and proteins such as MMPs (collagen breakdown), which will damage the extracellular matrix and weaken the bone structure. This is particularly the case in osteoporosis. Rosehip extract, thanks to its antioxidant effects, helps to regulate this process and thus increase the mineral density of the bone. It will also stimulate the differentiation of osteoblasts (formation of bone tissue), as well as the synthesis of collagen.36
Find out more about rosehip
Vitamins C, E, B3, K2, D3
The health benefits of vitamin C are well established, as it supports almost all the functions of our body. In the joints, vitamin C is an important regulator of cartilage and bone metabolism, in particular by influencing the differentiation of chondrocytes (cartilage cells) and osteoblasts (cells that form bone tissue).55 A significant increase in the number of collagen fibres was also observed as well as an acceleration in the healing of fractures.56 Vitamin C is key to maintaining healthy joints and preventing osteoarthritis and inflammation. 57
In fact, taking vitamin C reduces cartilage loss and prevents the appearance of osteoarthritis by reducing inflammation, oxidative stress, cell death and the synthesis of collagen-degrading MMPs.58 More specifically, regular use of vitamin C could reduce the risk of developing osteoarthritis by 11% (but not really stop its progression)59 and limit damage to the spinal cord of the knee as well as the size of the bone plateau, which are important elements in joint pathologies.60 In addition, there is an association between vitamin C deficiency and acute and chronic musculoskeletal pain, whereas its supplementation could reduce it and improve the patient’s quality of life.61 Vitamin C therapy reduces pain and the use of painkillers in people with early osteoarthritis while increasing the quality of life for everyone.57 It is also useful for reducing pain (Complex Regional Pain Syndrome Type I) after a fracture62 and limits the drop in blood vitamin C observed after arthroplasty surgery and the risk of arthrosfibrosis.63 According to EFSA, it is necessary for the normal functioning of cartilage and bone and protects against oxidative stress.*
Although some results are conflicting regarding the properties of vitamin D to relieve the symptoms of osteoarthritis, vitamin D supplementation may have been associated with a significant slowing down of knee abnormalities (joint structure and cartilage composition).64 It has also increased the strength and performance of the affected joint as well as the overall quality of life. Inflammation and oxidative damage in these patients were also significantly reduced, improving protein and DNA function.65,66 On the contrary, a vitamin D deficiency seems to be a risk factor for osteoarthritis.65,67 In addition, taking vitamin D may limit pain, which can be exacerbated by a deficiency.68 Concerning rheumatoid arthritis, it seems that many patients have a vitamin D deficiency, which could be related to the severity of the disease.69,70 In addition, vitamin D supplementation may limit musculoskeletal pain and prevent osteoporosis for these patients.69 Indeed, vitamin D is an important mediator and is involved in the regulation of various (mostly adaptive) immune responses and inflammation, essential roles in autoimmune diseases such as arthritis.71 According to EFSA, it is necessary for the normal maintenance of bones and calcium levels, and together with calcium can reduce bone demineralisation leading to osteoporotic fractures.*
Vitamin E is a powerful antioxidant and anti-inflammatory. It can therefore mitigate oxidative stress, which is one of the mechanisms that can lead to and accentuate the biomolecular degeneration of the joint causing osteoarthritis.72,73 It can also limit inflammation in the synovial fluid and cartilage, as well as pain.74, 75 Studies have pointed out that people suffering from osteoarthritis are often deficient in vitamin E, whereas its supplementation may limit the risks and delay the progression of osteoarthritis, thanks to different mechanisms (antioxidants, hormonal, immune, vascular, maintaining skeletal muscles, regulating cellular metabolism…).72,76 Similarly, it can prevent joint destruction, particularly by calming inflammation, in models of rheumatoid arthritis.77 According to EFSA, it protects against oxidative stress.*
Vitamin K is involved in the mineralisation of bone and cartilage, as well as in the regulation of the genes of the articular cartilage matrix and certain enzymatic reactions.78 People who are deficient in vitamin K are at greater risk of damage to cartilage and subchondral bone, which can lead to osteoarthritis and other joint diseases,78–81 whereas an adequate daily intake would appear to be protective.82 For vitamin K deficient people with osteoarthritis, taking vitamin K benefits the joints.83 Also, the intake of enough combined vitamins K and D allows an increase in walking speed and the ease of getting up from a chair for people with knee osteoarthritis.84 Vitamin K is of course also essential for good bone health, affecting bone strength and metabolism, notably by promoting the activation of bone-forming cells (osteoblasts) and proteins that mineralise the extracellular bone matrix.85 In addition to its role in mineralization, vitamin K seems to have an anti-inflammatory action, very useful for many chronic diseases (cardiovascular, osteoarthritis, osteoporosis…).86,87 In particular, it could reduce the level of inflammatory CRP in patients with rheumatoid arthritis. A clinical study has highlighted the improvement of the disease (less inflammation and proteins destroying the extracellular matrix) after 3 months of vitamin K intake.88 According to EFSA, it is necessary for the normal maintenance of bones.*
Although little studied, B vitamins may also be involved in bone health. Vitamin B3, also known as niacin, is effective in reducing oxidative stress,89,90 often very present in skeletal diseases. It could therefore play a role in the symptoms of osteoarthritis, improving the condition of the joint.91,92
Minerals (zinc, manganese, copper, selenium, calcium)
Zinc is a powerful antioxidant and is involved in the proliferation of chondrocytes (cartilage cells). Thus, zinc supplementation could prevent the progression of osteoarthritis.93 Similarly, zinc deficiency appears to correlate with the inflammation and progression of rheumatoid arthritis94,95, while zinc supplementation may reduce pain, stiffness, swelling, inflammation and pain medication in patients with psoriatic arthritis.96 Zinc also seems to play an important role in preventing and even curing osteoporosis, as it stimulates bone mineralisation and bone formation by osteoblasts and inhibits bone resorption by osteoclasts.97,98 The recommended daily dose of zinc is 10mg/d. Too much zinc can cause nausea or headaches. According to the EFSA, it is necessary for the normal maintenance of bones and protects against oxidative stress.*
Manganese and copper are essential for bone metabolism as they are co-factors for several enzymes. Their supplementation increases the mineral density of the bones, making them valuable allies against osteoporosis.99,100 These minerals, particularly when combined with zinc, are very effective in limiting bone loss.98
Manganese can play an important role in the formation of cartilage and bone collagen and in the mineralisation of bone. It is also present in several antioxidant enzymes, which help limit free radicals.101 These antioxidant properties are particularly important for limiting inflammation in rheumatoid arthritis: it can act on the enzymes that regulate the amount of nitric oxide, particularly in the synovial fluid.102 Manganese, especially when combined with glucosamine and chondroitin, seems to be effective in alleviating the symptoms of osteoarthritis,103 in particular by modulating the metabolism of cartilage and synovial fluid.104 Manganese is also involved in the proper functioning of the immune system, the regulation of blood sugar levels, digestion, reproduction, bone growth…101 According to EFSA, it is necessary for the normal maintenance of bones and the formation of connective tissue, and protects against oxidative stress.*
Copper is equally important for bone strength and mineralization, and for the prevention of skeletal abnormalities and osteoporosis. In particular, it helps promote collagen chain bonding, limits free radicals by being a co-factor of antioxidant enzymes and directly inhibits bone resorption by osteoclasts.98 A copper deficiency can therefore lead to skeletal problems such as osteoporosis, as well as dermatological, immune and cardiovascular problems, but too much copper consumption has also been associated with a high risk of fractures.105 According to EFSA, it is necessary for the normal maintenance of connective tissue and protects against oxidative stress.*
Attention, harmful effects, especially neurological, can occur with a consumption of more than 11mg/day for manganese (2mg = ADI) and gastrointestinal with more than 10mg/day of copper (1mg = ADI).100
Calcium is the mineral known per excellence for the health of our bones and the maintenance of a good mineralization of the bone mass.98 Nevertheless, the experts stress the importance of combining it with vitamin D to increase bone mineral density and limit osteoporosis as well as certain fractures, although the results in the latter case are more mixed.106,107 Indeed, vitamin D regulates the intestinal absorption of calcium.108 Studies suggest that it is even more effective to take them with zinc, copper and manganese to increase bone health.98 Good calcium intake also seems to be correlated with a reduced risk of knee osteoarthritis,109 which could be explained by the inhibition of cartilage cell (chondrocyte) death by blocking inflammatory cell pathways (COX-2).110 According to the EFSA, it is necessary for the normal maintenance of bones and, combined with vitamin D, can reduce bone demineralisation leading to osteoporotic fractures.*
Nevertheless, taking too much calcium (above 1000mg/day in addition to that in a normal diet) can lead to cardiovascular, renal or gastrointestinal complications.111
Selenium is an essential nutrient for selenoproteins, which function as antioxidants that regulate inflammation and influence bone metabolism (proliferation of osteoblasts and inhibition of bone-resorbing osteoclasts). 98,112 Good selenium intake was associated with good bone mineralisation.113,112 Its properties highlight how it could provide some protection against osteoarthritis, rheumatoid arthritis, osteoporosis and bone damage from oxidative stress.98,114 Concerning osteoarthritis, selenium combined with vitamins A, B2, B6, C and E would make it possible to limit the disease, in particular by reducing oxidative stress.115 One study pointed out that combining selenium with vitamins C and E would be even more effective in preventing bone damage leading to osteoporosis.116 On the contrary, a selenium deficiency increases bone resorption and decreases the volume and the mineral density of the bone. In this sense, people with selenium deficiency are more at risk of osteoporosis and osteoporotic fractures.98 Similarly, selenium deficiency has been correlated with the risk of rheumatoid arthritis, in which inflammation and oxidative stress play an important role.117 According to EFSA, it protects against oxidative stress.*
Selenium also has an important role in the proper functioning of the immune, musculoskeletal, nervous, endocrine, cardiovascular and reproductive systems.118 Selenium consumption in Europe is often too low,119 the recommended dose of selenium is around 55mg/day, but intakes above 400mg/day can be toxic.120
Plants : Gentian, edelweiss, melon
Alpine plants traditionally used for their health benefits, the properties of gentian and edelweiss are impressive.
Gentian has an analgesic effect which helps to reduce persistent inflammatory pain. It can in fact modulate the transmission of pain and reduce the expression of certain pain receptors in the brain. This effect on the central nervous system could be due to the different compounds that gentian contains (gentiopicrosides, swertiamarine, sweroside). Gentian may also improve endurance performance.121,122 It has traditionally been used to treat inflammation of the joints, particularly in rheumatoid arthritis. By inhibiting COX-2 and the secretion of inflammatory cytokines, it indeed appears to be efficient.123
Taking edelweiss orally can have many health benefits: it is anti-inflammatory, analgesic and antioxidant.124,125 Its anti-inflammatory power can be seen in particular with the reduction in the secretion of inflammatory cytokines and the inhibition of chemotaxis, i.e. the reduction in the accumulation of leukocytes (white blood cells) in the inflamed tissues.124,125
To find out more about gentian and edelweiss
The properties of the melon, even though it does not come from the Alps, are not to be neglected either. Indeed, it is rich in SOD, an antioxidant enzyme essential to our proper functioning. Swiss Alp Health uses a special extract, Extramel®, which is highly dosed in SOD. Several studies have highlighted the antioxidant and anti-inflammatory properties of melon, reducing the production of inflammatory cytokines and free radicals, as well as stimulating the production of the anti-inflammatory cytokine (IL-10) by macrophages.126 It is also useful for limiting mental and muscular fatigue and stress.127
Osteoarthritis is often associated with an increase in oxidative stress,128 as this can lead to different inflammatory responses, cartilage cell death, degradation of the extracellular matrix, dysfunction of the subchondral bone, increased pain etc.129,130 It has been shown that the genes producing SOD are poorly expressed in people with osteoarthritis131,132 but not in other people of the same age, which encourages the oral consumption of SOD,133,134 especially as the SOD properties of the melon are preserved during digestion.126 In rats, the ingestion of SOD can reduce pain, joint disturbances and the production of inflammatory cytokines and thus help to protect the cells of the articular cartilage.135 In horses, the ingestion of SOD can limit oxidation and inflammation in the joints, preserve the integrity of the cartilage and alleviate joint pain.136
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The information published on www.swiss-alp-nutrition.ch does not claim to be complete and is not a substitute for individual medical advice or treatment. It cannot be used as an independent diagnosis or to select, apply, modify or discontinue treatment of a disease. In case of health problems, it is recommended to consult a doctor. Any access to www.swiss-alp-nutrition.ch and its contents is at the user’s own risk.
Food supplements should not be used as a substitute for a varied diet. The recommended daily allowance should not be exceeded. In general, food supplements are not suitable for pregnant and nursing women, children and adolescents. Keep out of reach of children.
* EFSA : official health claims from the European Food Safety Authority. An EFSA health claim is a statement about a relationship between a food and health. The European Commission authorises various health claims as long as they are based on scientific evidence.
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