Musculoskeletal health encompasses the functionality of the body’s locomotor system, comprising muscles, bones, joints, and surrounding connective tissues. Conditions affecting this system are often marked by persistent pain, reduced mobility, and impaired dexterity, thereby hindering individuals’ ability to engage fully in work and societal activities. Pain originating from musculoskeletal structures represents the most prevalent form of non-cancer-related pain.
These conditions are pertinent across all stages of life, from childhood through old age, ranging from acute incidents like fractures and strains to chronic ailments such as primary low back pain and osteoarthritis. They encompass a variety of joint-related issues including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, and spondyloarthritis.
Furthermore, musculoskeletal conditions represent a significant portion of the global demand for rehabilitation services. Individuals affected by these conditions also face an increased risk of developing mental health disorders.
Joint pain can severely impact the quality of life. Joints can incur damage through various means: surpassing their natural range of motion (e.g., causing an ACL tear in the knee), enduring repetitive stress or pressure on the surrounding areas (e.g., from repetitive movements, poor positioning, or excessive load on a shoulder joint), or undergoing gradual deterioration due to factors like ageing, disease, or genetic predispositions. The combination of these potential causes, often intertwined and intersecting, complicates the management of joint pain. Additionally, the intricate nature of joint tissue further adds to the challenge of addressing these issues effectively.
A food supplement’s role in joint health is very important in terms of preventing joint damage and also to slow down degenerative and ageing processes in joints.
Joints are made of:
- Articular cartilage: Smooth, slippery tissue covering the ends of bones within a joint, which helps reduce friction and allows for smooth movement.
- Synovial membrane: A thin layer of tissue that lines the joint capsule and produces synovial fluid, which lubricates the joint and provides nutrients to the cartilage.
- Joint capsule: A fibrous structure that surrounds the joint, consisting of tough connective tissue that helps hold the bones together and maintain joint stability.
- Ligaments: Strong bands of fibrous tissue that connect bones to other bones, providing stability and limiting excessive movement in the joint.
- Tendons: Fibrous cords of tissue that connect muscles to bones, transmitting forces generated by muscle contraction to move the joint.
- Meniscus (in certain joints): Cartilaginous structures found in some joints, such as the knee, that act as shock absorbers and help distribute forces evenly across the joint surfaces.
Ingredients helping maintain healthy and functional articular cartilage
Supplements for joint health with a focus on articular cartilage often contain glucosamine, chondroitin, hyaluronic acid, Boswellia serrata extract, bromelain and many more.
Glycosaminoglycans (GAG-s)
The extracellular matrix (ECM) serves as a gel-like substance occupying the intercellular spaces within tissues, facilitating cell cohesion and serving as a conduit for the diffusion of vital nutrients and oxygen to individual cells. Comprised of fibrous proteins such as collagen, elastin, fibronectin, and laminin, as well as heteropolysaccharides known as glycosaminoglycans (GAGs), the ECM forms a complex network essential for tissue structure and function.
Chondroitin, classified as a glycosaminoglycan, comprises elongated polysaccharide chains characterized by a repeating disaccharide pattern. Typically consumed in the form of chondroitin sulfate supplements, it occurs naturally within cartilage. In this tissue, chondroitin plays a pivotal role in thwarting tissue degradation and furnishing vital mechanical reinforcement to the joints.
Chondroitin is frequently employed to mitigate the symptoms associated with osteoarthritis, often in conjunction with glucosamine. Among individuals afflicted with osteoarthritis, chondroitin supplementation has been observed to potentially alleviate pain and joint stiffness, as well as potentially impede the advancement of the condition1.
Dosage recommendations range from 800 mg–1200 mg per day. This may be taken as a single dose or in 2–3 400mg doses.
Glucosamine sulphate has studies that prove its effect on pain.
Glucosamine sulphate is usually dosed up to 1500 mg in medicinal products but also, in food supplements. One of the limiting factors in formulating glucosamine is dosage, if you want to achieve 1,5 g of the mentioned daily dosage.
Usually, it is recommended to be in powder form in sachets since otherwise 4 tablets per day are a bad choice in terms of compliance for food supplement users.
Hyaluronic acid (HA) is a large mucopolysaccharide that is found naturally throughout the body and in high concentrations in the skin, the joint fluid, and the eye. (Figure 1) It is produced from animal sources or by bacterial fermentation.
In its native form, HA appears as a very long polymer, called high-molecular weight HA (HMWHA)]. However, under certain conditions, the molecule can be broken down into small fragments, called low-molecular weight HA (LMWHA). HMWHA, usually greater than 1000 kDa, is present in intact tissues and is antiangiogenic and immunosuppressive, while smaller polymers indicate signs of distress and are potent inducers of inflammation and angiogenesis. Most cells in the human body can synthesize HA during certain processes in their cell cycle.
HA differs from other GAGs because it is not sulphated and is not synthesised by Golgi enzymes in association with proteins; it is produced in the inner face of the plasma membrane, without any covalent binding to a protein nucleus, by hyaluronan synthases (HAS-1, HAS -2 and HAS-3). These three proteins place the HA molecules in the extracellular space through pore-like structures, along the length of the polymeric chain, repeatedly adding D-glucuronic acid and N-acetyl-D-glucosamine (Figure 2), giving rise to molecules of different sizes. This unique synthesis mechanism, which allows the molecule to be secreted during its production, is essential; otherwise, due to its enormous size, the cells would be destroyed. Incorrect deregulation of the expression of HAS genes results in abnormal HA production and, therefore, an increased risk of pathological events, altered cellular responses to injuries and aberrant biological processes. It has also been established that growth factors, such as epidermal growth factor (EGF) or keratinocyte factor, increase the rate of HA synthesis.
Due to its molecular structure at a neutral pH, HA attracts water molecules and can contain up to 10,000 times its weight in water. The viscous gel formed by the HA matrices lubricates the joints and acts as a buffer for the surrounding tissues, as well as participating in tissue regeneration and remodelling processes, for example, during the healing process2.
For oral supplementation, the recommended dosage is 120 mg per day, with supplements usually available in either 60 mg or 120 mg tablets.
Frankincense Boswellia serrata
Derived from the Boswellia serrata tree, gum resin has long been recognized for its potential in promoting joint health. Its active compounds, including boswellic acids, possess anti-inflammatory properties that can help alleviate symptoms associated with conditions like osteoarthritis and rheumatoid arthritis. Research suggests that Boswellia extracts may reduce pain, stiffness, and inflammation in joints, enhancing mobility and overall quality of life for individuals with joint-related issues. Incorporating Boswellia supplements as part of a comprehensive approach to joint care may offer significant benefits, providing a natural and alternative option for managing joint discomfort and promoting long-term joint health.
The gum resin is extracted from a well-known herb Boswellia serrata Roxb. ex Colebr. (Family: Burseraceae), also called Indian frankincense or Salai guggul, has been used in traditional Ayurvedic medicine in India for centuries as a remedy for the treatment of chronic inflammatory diseases, including OA.
The β-configured pentacyclic triterpene acids in B. serrata include 3-acetyl-11-keto-β-boswellic acid (AKBBA), 11-keto-β-boswellic acid (KBBA), β-boswellic acid (BBA), and 3-acetyl-β-boswellic acid (ABBA), representing major ingredients.
In following study, BSE tablets, each tablet containing the BSE extract of 169.33 mg with a mean value of 87.3 mg of total β-boswellic acids, corresponding to the four major β-boswellic acids, namely, AKBBA (53.27 mg), BBA (20.83 mg), KBBA (7.11 mg), and ABBA (6.06 mg), were given twice a day. Thus, the selected dosage of BSE, equivalent to 87.3 mg of total β-boswellic acids per tablet twice a day (174.6 mg of total β-boswellic acids per day), was safe.
A double-blind, placebo-controlled human trial was conducted to evaluate the safety and efficacy of a standardised oral supplementation of Boswellin®, a novel extract of Boswellia serrata extract (BSE) containing 3-acetyl-11-keto-β-boswellic acid (AKBBA) with β-boswellic acid (BBA). A total of 48 patients with osteoarthritis (OA) of the knee were randomized and allocated to the BSE and placebo groups for intervention. Patients were administered BSE or placebo for 120 days. The trial results revealed that BSE treatment significantly improved the physical function of the patients by reducing pain and stiffness compared with placebo. Radiographic assessments showed improved knee joint gap and reduced osteophytes (spur) confirming the efficacy of BSE treatment. BSE also significantly reduced the serum levels of high-sensitive C-reactive protein, a potential inflammatory marker associated with OA of the knee. No serious adverse events were reported. This is the first study with BSE conducted for 120 days, longer than any other previous clinical trial on patients with OA of the knee. The findings provide evidence that biologically active constituents of BSE, namely, AKBBA and BBA, act synergistically to exert anti-inflammatory/anti-arthritic activity showing improvement in physical and functional ability and reducing pain and stiffness.
Examination of radiological X-ray images revealed reduced joint space due to loss of articular cartilage and osteophyte formation in OA of the knee patients in the placebo group. On the other hand, the OA of the knee patients in the BSE treatment groups showed significant improvements on the final visit (120 days). A distinct change in the OA condition could be seen where the gap between the knee joints increased significantly with a sharp decrease in osteophytes (spur) in subjects (Figure 3).
The present clinical trial demonstrated the safety and efficacy of oral supplementation of BSE containing 30% AKBBA and other bioactive β-boswellic acids, namely, BBA, KBBA, and ABBA, in newly diagnosed or untreated patients with OA of the knee.
Earlier, the efficacy of boswellic acid-containing product (Boswellin®) in combination with Curcumin C3 Complex® and ginger extract was demonstrated in the management of OA.
The current findings are also consistent with earlier studies indicating that BSE comprising β-configured derivatives of boswellic acids are specific nonredox inhibitors of 5-LOX and hence inhibit leukotriene biosynthesis and reduce the pain associated with joint stiffness and physical discomfort.
FIGURE 4 Mechanisms of action of β-boswellic acids against osteoarthritis (OA) of the knee. Biologically active constituents of BSE, namely, β-boswellic acid (BBA) and 3-acetyl-11-keto-β-boswellic acid (AKBBA), act synergistically to exert anti-inflammatory/anti-arthritic activity to reduce joint pain and improve physical functional ability in patients with OA of the knee. ABBA: 3-acetyl-β-boswellic acid; IL: interleukin; KBBA: 11-keto-β-boswellic acid; TNF-α: tumor necrosis factor alpha
This study has limitations- it is a pilot study with a small group of subjects. Despite some of these limitations, the present clinical trial demonstrated the safety and efficacy of BSE (Boswellin®) in patients with OA of the knee. Despite some of these limitations, the present clinical trial demonstrated the safety and efficacy of BSE (Boswellin®) in patients with OA of the knee. The findings from the present study provide clinical evidence to support that biologically active components of BSE, specifically AKBBA and BBA, acted synergistically to exert anti-inflammatory/anti-arthritic activity efficaciously in reducing joint pain and improving physical functional ability (Figure 4). No serious adverse events were observed, thus supporting the pharmacological safety of BSE (Boswellin®) to be considered a viable candidate for the treatment of OA of the knee3.
Taking into account this study and other relevant studies, frankincense can be considered a very valuable asset in preserving joint function through different challenges (EFSA on hold claims in Table 1).
Bromelain
Bromelain is a mixture of proteolytic enzymes found in the pineapple plant (Ananas comosus). It is particularly concentrated in the stem and juice of the fruit. Bromelain has been used for centuries as a traditional medicine in Central and South America, where pineapples are native. Bromelain can be actively absorbed from the intestine and keep its bioactivity. Accurate quantification of bromelain enzymatic activity units, such as GDU and MCU, is essential for evaluating the potency and efficacy of bromelain-containing products. These standardized measurements facilitate informed decisions regarding supplement selection and dosage, particularly in therapeutic contexts where bromelain’s proteolytic and anti-inflammatory properties are sought after.
Gelatin Digesting Units (GDU) represent the capacity of bromelain to hydrolyze gelatin under specific conditions. This measurement is crucial for assessing the enzyme’s proteolytic activity. GDU activity of the extract is important for the dosage of the extract in the food supplement.
A following study demonstrated that bromelain effectively reduces mild acute knee pain and enhances overall well-being in a dosage-dependent manner among healthy adults. There is early clinical evidence supporting its potential in alleviating symptoms of osteoarthritis and rheumatoid arthritis.
This study aimed to explore bromelain’s effects on mild acute knee pain lasting less than three months in otherwise healthy adults. Participants were randomly assigned either 200 mg or 400 mg of bromelain daily for one month and completed validated questionnaires assessing knee health and psychological well-being at the beginning and end of the intervention. Seventy-seven participants completed the study. Both treatment groups showed significant reductions in knee pain symptoms compared to baseline, with greater improvements observed in the high-dose group. Moreover, psychological well-being significantly improved in both groups, with a stronger effect seen in the high-dose group.
These findings suggest that bromelain may effectively alleviate physical symptoms and enhance overall well-being in individuals experiencing mild knee pain, with its efficacy potentially increasing with higher doses. Future research involving double-blind, placebo-controlled studies is needed to further validate these results4.
Research suggests that some people may experience allergic reactions when using bromelain. People who are allergic to pineapple are particularly vulnerable5.
Due to its good biological functions, lack of systemic cytotoxicity, and often excellent benefits that it offers, bromelain has been permanently used in many industries, such as cosmetology, pharmacy, food, and biotechnology. The commercial use of bromelain has contributed to the development of effective methods for extracting the enzyme from the pineapple stem, and the resulting preparations are characterized by ultra-purity. Pineapple stems are often considered food waste products, so their usage for bromelain extraction is very valuable.
Recent studies prove that using bromelain in combination therapy with other nutraceuticals, such as rutin, trypsin, or turmeric, results in significantly enhanced efficacy in the treatment of degenerative joint pain diseases6.
Bromelain as a raw material for formulating food supplement products can be challenging. This is why microencapsulation is recommended.
Microencapsulation of bromelain offers several advantages over its traditional powder form. One of the key benefits is improved stability. The microencapsulation process can enhance the stability of bromelain, protecting it from environmental factors such as heat, light, and oxygen that can degrade the enzyme. Another advantage is the potential for controlled release. Microencapsulation allows for the controlled release of bromelain, ensuring that it is delivered to the specific site in the digestive system where it can be most effective. This process can also improve the bioavailability of bromelain, increasing the amount that is absorbed into the body and thereby enhancing its effectiveness. Lastly, microencapsulation can mask the taste and odour of bromelain, making it more palatable. These advantages make microencapsulated bromelain a promising option for therapeutic applications.
Conclusion
In conclusion, the multifaceted nature of musculoskeletal health underscores the importance of proactive measures to address joint pain and maintain overall well-being. Incorporating supplements containing key ingredients like glucosamine, chondroitin, hyaluronic acid, Boswellia serrata extract, and bromelain can offer significant relief and support joint function. Furthermore, sustainable practices in extraction processes, such as those seen with bromelain, alongside advancements like microencapsulation, not only enhance efficacy but also contribute to long-term viability and environmental stewardship. By incorporating targeted food supplements into everyday routine, patients can better navigate the complexities of musculoskeletal health and pave the way for improved quality of life.
References:
- Bruyère O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49(3):337-350. doi:10.1016/j.semarthrit.2019.04.008
- Marinho A, Nunes C, Reis S. Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules. 2021;11(10):1518. Published 2021 Oct 15. doi:10.3390/biom11101518
- Majeed, Muhammed, et al. “A pilot, randomized, double‐blind, placebo‐controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee.” Phytotherapy Research 33.5 (2019): 1457-1468.
- Walker, A. F., Bundy, R., Hicks, S. M., & Middleton, R. W. (2002). Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine : international journal of phytotherapy and phytopharmacology, 9(8), 681–686. https://doi.org/10.1078/094471102321621269
- Knox, S., Lang, D., & Hoyt, A. (2019). The many flavors of pineapple reactions. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 123(5), 519–521. https://doi.org/10.1016/j.anai.2019.08.001
- Hikisz, P., & Bernasinska-Slomczewska, J. (2021). Beneficial Properties of Bromelain. Nutrients, 13(12), 4313. https://doi.org/10.3390/nu13124313
