Bone consists of a fibrous protein called collagen. Collagen is arranged in long strands or bundles. It has small amounts of protein polysaccharides and glycosaminoglycans chemically bound to the protein and dispersed within and around the collagen fiber bundles.

Organic material constitutes fifty percent of the volume and thirty percent of the dry weight of the bone. Minerals, primarily calcium and phosphate, are present in intercellular composite form.

Mineral crystals are responsible for hardness and rigidity and strengthen the bone. Collagen fibrils provide elasticity and intrinsic tensile strength. The intimate association between minerals and collagen confers the bones their general properties.

Supplements support the management of symptoms and promote joint health. A well-rounded approach, including a balanced diet, regular exercise, and proper medical guidance, is crucial for effectively managing arthritis and musculoskeletal injuries. Supplements cannot substitute for medical treatments prescribed by healthcare professionals.

Supplements help provide the body with vital nutrients for the health and maintenance of joints, cartilage, and bones. For instance, adequate calcium and vitamin D intake is crucial for maintaining bone density and preventing osteoporosis. Essential vitamins and minerals, including Vitamin K, are important in bone metabolism and overall musculoskeletal health.

They contribute to the formation of collagen, a key component of connective tissue. Tissue health is critical to maintaining the structural integrity of joints and the musculoskeletal system. In autoimmune forms of arthritis, like rheumatoid arthritis, supplements help module the immune response.

Inflammation is a common factor in musculoskeletal injuries and arthritis. The anti-inflammatory properties of select supplements help to alleviate pain and reduce swelling. Pain management is important. Supplements that contain molecules with analgesic properties contribute to pain management and minimize distress from musculoskeletal injuries.

Specific supplements improve joint function by supporting synovial fluid's lubrication and shock-absorbing properties. In the previous chapter, we provided an overview of the role of nutrients, selected herbs, and supplements. We will continue to expand on this subject in this chapter.

Understanding supplements

Supplements are dietary products that contain one or more nutrients. These nutrients can include vitamins, minerals, amino acids, herbs, botanicals, enzymes, and other substances. Supplements come in various forms, including liquids, powders, tablets, pills, and capsules. These nutrients play an important role in maintaining healthy body functions.

Vitamins

Vitamins are co-factors and coenzymes essential for various enzymatic reactions within cells. Vitamins D, K, C, A, E, B6, and B12 are the most important for maintaining a healthy musculoskeletal system.

Vitamin D

Vitamin D is a fat-soluble vitamin that plays a crucial role in various physiological processes in the body. There are two main forms of vitamin D: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is primarily obtained from plant sources, while D3 is synthesized in the skin when exposed to ultraviolet B (UVB) sunlight. 

Our bones are a storage site for calcium and phosphorus. Proper calcium levels are crucial for maintaining bone density and preventing osteoporosis. Vitamin D plays a pivotal role in calcium homeostasis. It enhances calcium absorption from the small intestine, ensuring an adequate amount of calcium is absorbed into the bloodstream. 

Vitamin D is essential for developing and maintaining healthy bones. It promotes bone mineralization by supporting the deposition of calcium and phosphorus. Inadequate vitamin D can lead to soft and brittle bones, increasing the risk of fractures and bone disorders.

Parathyroid, vitamin D, and calcitonin regulate the process. The parathyroid glands release the parathyroid hormone (PTH). The regulation happens mainly in the gut, kidneys, and bone.

Calcium

Calcium metabolism is the movement and regulation of calcium ions in and out of the body. Bones lose calcium when its levels in the blood drop, and it is deposited in the body when the calcium levels in the blood are high. The optimum calcium level is between 8.6 and 10.3(mg/dl—milligrams per deciliter). The mineral is found in the blood plasma, the extracellular and intracellular fluids, and the bone. 

Calcium is a major bone mineral. It is found in bones in the form of hydroxyapatite crystals. These crystals provide strength and rigidity to bones, contributing to their structural integrity. Adequate calcium intake is crucial during periods of bone growth, such as childhood and adolescence. It supports the development of strong and dense bones. Calcium continues to play a role in maintaining bone density throughout adulthood.

The mineral is involved in bone remodeling, wherein new bone tissue replaces old bone tissue. This dynamic process helps maintain bone strength and helps the body adapt to changing mechanical demands. Sufficient calcium levels are necessary for the optimal bone remodeling process.

Calcium is essential for muscle contraction. Calcium ions are released within the muscle cells each time a nerve signal triggers a muscle to contract. Calcium and proteins in muscle fibers allow for the sliding of filaments, enabling muscle contraction. Our body needs adequate calcium levels to function and prevent muscle weakness. Calcium, therefore, plays a role in nerve function. It influences the transmission of nerve signals. It is involved in the release of neurotransmitters at nerve endings.

Calcium is required to activate clotting factors that lead to the formation of blood clots.  The clotting process helps prevent excess bleeding. It plays an important role in tissue repair.

We obtain calcium from dairy products, leafy green vegetables, fortified plant-based milk alternatives like soy and almond milk, fortified foods like cereals and orange juice, and fish with edible bones such as canned salmon and sardines.

Vitamin D facilitates and is essential for calcium absorption. Adequate vitamin D levels enhance the body’s absorption and utilization of calcium.

Calcium needs vary throughout the life. Age, gender, and activity level influence the body's calcium requirements.

Vitamin D has immunomodulatory effects. It influences the activity of immune cells and cytokines. A vitamin D deficiency is associated with an increased risk of autoimmune diseases. It is also involved in regulating cell growth, proliferation, and differentiation. Proper vitamin D levels are essential for normal cellular function.

Phosphorus and calcium play a significant role in maintaining a healthy musculoskeletal system. Phosphorus is a primary component of hydroxyapatite, the mineral complex that strengthens bones and rigidity. Hydroxyapatite consists of calcium phosphate crystals. A proper balance of calcium and phosphorus is essential for giving bones optimal strength and rigidity.

Phosphorus

Phosphorus is a key component of adenosine triphosphate (ATP), which serves as cells' primary energy currency. ATP releases energy when its phosphate bonds are broken during cellular processes. It is involved in muscle contraction and contributes to the energy metabolism necessary for muscle function and physical activity.

Minerals are the structural component of nucleic acids (DNA and RNA) in various cellular compounds, such as phospholipids in cell membranes. Nucleic acids are essential for cell growth, repair, and division. Phosphorus helps maintain proper pH levels, which is crucial for various biochemical reactions and enzymatic activities. It is closely regulated by the kidneys, preventing imbalances in phosphorus levels. These imbalances will impact the entire body, including the musculoskeletal system.

Calcium and phosphorus are the main minerals in the bones. Low phosphorus levels can stimulate the parathyroid glands to release parathyroid hormone (PTH). PTH increases the absorption of phosphorus from the kidneys and intestines. When vitamin D is insufficient, PTH levels may rise, leading to increased phosphorus reabsorption by the kidneys.

An imbalance between phosphorus and calcium is important to maintain bone health. Adequate vitamin D levels are important for phosphorus absorption from the digestive tract.

Phosphorus is available in protein-rich foods such as meat, poultry, eggs, dairy products, legumes, nuts and seeds, whole grains, and processed foods that contain phosphorus-containing food additives.  

Vitamin D receptors are found in various tissues throughout the body. Its deficiency has been associated with muscle weakness. Maintaining adequate vitamin D levels supports muscle strength and reduces the risk of falls, especially in older adults. (Bouillon R et al., 2008)

Vitamin D3 is synthesized in the skin when exposed to UVB sunlight. UVB radiation converts 7-dehydrocholestrol in the skin into pre-vitamin D3, which undergoes further transformations to become vitamin D3.

Vitamin D can be obtained from fatty fish (salmon, mackerel), fortified dairy products, egg yolks, and vitamin D supplements.  In the liver, vitamin D undergoes hydroxylation to form 25-hydroxyvitamin D, the main circulating form of vitamin D. In the kidneys; it undergoes further hydroxylation to become the active form 1,25-dihydroxy vitamin D, also known as calcitriol.

Calcitriol acts on target tissues, such as intestines, bones, and kidneys. In the intestines, it enhances the absorption of calcium. It supports bone mineralization in the bones, and in the kidneys, it regulates calcium and phosphorus homeostasis.

Parathyroid hormone (PTH) stimulates calcitriol synthesis when calcium levels are low. It, in turn, increases calcium absorption, maintaining homeostasis. Vitamin D is a hormone in the body and plays a vital role in bone health and immune system regulation. (Guillot, X et al., 2010) Adequate exposure to the sun, dietary intake, and supplements when necessary are essential for optimal vitamin D levels. Excessive vitamin D intake can have adverse effects.

Vitamin K

Vitamin K plays a crucial role in various physiological processes and bone metabolism. There are two primary forms of vitamin K. The first is vitamin K1 (phylloquinone) from leafy green vegetables. Vitamin K2 (menaquinone), found in fermented foods and animal products, is the second form of this vitamin. Vitamin K is essential for proper blood coagulation and bone health.

The vitamin is a co-factor for enzymes that synthesize blood clotting proteins, especially clotting factors II (prothrombin), VII, IX, and X. Its deficiency impairs clotting, leading to an increased risk of bleeding and hemorrhage.

Vitamin K synthesizes proteins, such as osteocalcin, necessary for bone mineralization. Proper Vitamin K levels contribute to bone health. It ensures calcium is incorporated into the bone matrix and promotes bone strength and density.  The vitamin also plays a role in preventing the calcification of blood vessels by regulating the activity of matrix Gla-protein (MGP), an inhibitor of vascular calcification. It is important to maintain the flexibility and health of blood vessels.

Vitamin K is a co-factor for the enzyme gamma-glutamyl carboxylase. The enzyme catalyzes the carboxylation of certain glutamate residues in precursor proteins, converting them into active forms. In the liver, vitamin K-dependent clotting factors (II, VII, IX, X) undergo carboxylation to become functional. The process is essential for forming blood clots in response to injuries.

Osteocalcin, a vitamin K-dependent protein, is synthesized by osteoblasts (bone-forming cells). Vitamin K promotes the incorporation of calcium into the bone matrix, contributing to bone mineralization. (Neve A et al., 2012)

This vitamin also helps maintain vascular health. Vitamin-K-dependent proteins inhibit vascular calcification in blood vessels, preventing calcium deposition in the arterial walls.

Vitamin K1 can be obtained from green leafy vegetables such as kale, spinach, broccoli, and Brussels sprouts. Vitamin K2 is found in fermented foods and animal products like cheese, eggs, and meat. Vitamin K is fat-soluble, and dietary fat is necessary for its absorption. Gut bacteria produce a form of vitamin K, contributing to overall vitamin K status. 

Deficiency of this vitamin is rare. It can occur in certain conditions that affect fat absorption and liver function or in individuals on long-term antibiotic therapy. Vitamins are crucial for maintaining proper blood clotting, bone health, and overall vascular integrity.

Vitamin C

Vitamin C, also known as ascorbic acid, is an essential nutrient obtained through diet. It is found in fruits and vegetables, such as citrus fruits, strawberries, kiwis, bell peppers, and broccoli.

Vitamin C is an antioxidant that helps neutralize free radicals. Oxidant free radicals are unstable molecules produced as byproducts of normal metabolism and in response to environmental factors such as pollution and UV radiation. Vitamin C neutralizes these free radicals, helping protect cells and tissues from oxidative stress, which is one of the causes of aging and various chronic diseases.

The vitamin is essential for the synthesis of collagen. Collagen is a structural protein that forms connective tissue in the skin, bones, cartilage, and blood vessels. It provides strength and elasticity to tissues. Adequate Vitamin C is necessary for wound healing, maintaining skin integrity, and supporting the health of blood vessels.

Vitamin C enhances the function of the immune system. It promotes the production and function of white blood cells and contributes to the body’s ability to defend against infections and illnesses.

Vitamin C enhances the absorption of non-heme iron(details on this are available in Chapter 2) from the digestive tract. Non-heme iron absorption is less efficient, and iron deficiency is often observed in vegans and vegetarians. A combination of vitamin C in such diets will enable individuals to leverage the benefits of plant-based foods.

This vitamin has antiviral and antimicrobial properties. Its ability to support immune function protects it against viral and bacterial infections. It could help reduce the severity of respiratory diseases.

Vitamin C antioxidant action is because of its ability to neutralize free radicals, preventing them from damaging cellular structures that include DNA. It is a co-factor for enzymes. It is involved in the hydroxylation of proline and lysine residues in collagen precursor molecules. The process is crucial for the formation of stable collagen fibrils. Collagen fibrils are the basic building blocks of tendons. (LaPrada RF et al., 2018)

Vitamin C is sensitive to heat and light. Consuming various fresh fruits and vegetables will ensure an adequate intake of this vitamin. We can get vitamin C from citrus fruits, strawberries, kiwi, mangoes, papaya, bell peppers, broccoli, Brussels sprouts, spinach, and tomatoes.

Vitamin A

Vitamin A is essential for various physiological functions in the body. It has several forms, including retinol, retinal, and retinoic acid.

Retinol is the primary form of vitamin A found in animal products. It is the storage form of vitamin A in the liver. Retail converts to retinal and then to retinoic acid in the body. Foods rich in retinol include liver, fish liver oil, eggs, and dairy products.

Retinal is an intermediate form of vitamin A. It is derived from retinol and serves as a key component in the visual cycle within the retina. Retinoic acid is the active form of vitamin A. It plays a crucial role in cell growth. Retinoic acid is not commonly found in food. It is synthesized in the body from the retina. It is obtained in prescription medications and is used for skin ailments.

Vitamin A is found in animal products as preformed Vitamin A, primarily retinol, and in plant-based foods as provitamin A carotenoids, such as beta-carotene. Vitamin A, in the form of retinoic acid, has anti-inflammatory properties. It modulates immune responses, regulating the inflammatory processes associated with arthritis. Inflammatory arthritis conditions, such as rheumatoid arthritis, involve an overactive immune response. Vitamin A’s anti-inflammatory effects contribute to managing inflammation in joints.

The vitamin is involved in bone metabolism. It supports normal bone growth and maintenance. It influences osteoblast and osteoclast activity, which are essential for bone remodeling. It contributes to the overall health of bones and helps in bone density loss conditions such as osteoporosis.

In arthritis, where the immune system may be dysregulated, proper immune function is important. Vitamin A provides immune support and contributes to a balanced immune response. It supports the function of white blood cells.

Cartilage is crucial for joint flexibility and shock absorption. Preserving the integrity of cartilage is essential for preventing joint degradation in conditions like osteoarthritis.  Vitamin A is involved in the maintenance of connective tissues, including cartilage. (Yee MMF et al., 2021)

The vitamin influences cell growth, proliferation, and differentiation, all processes important for repairing and regenerating tissues in the musculoskeletal system. Joint tissue undergoes damage in arthritis. Vitamin A plays a positive role in supporting cell repair and regeneration and in overall musculoskeletal health.

We can obtain preformed vitamin A from liver, fish liver oil, eggs, dairy products, and provitamin A carotenoids from carrots, sweet potatoes, spinach, kale, apricots, mangoes, and other colored fruits and vegetables.

Vitamin E

Tocopherols and tocotrienols are two major groups of compounds that make up the vitamin E family. The four major forms of tocopherols are alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and delta-tocopherol. Alpha-tocopherol is the most biologically active form and is considered the primary form of vitamin E that meets human requirements. Tocotrienols share antioxidant properties with tocopherols and show lower biological activity.

Both molecules function as antioxidants, protecting cells and tissues from oxidative damage caused by free radicals. Tocopherols are found in various vegetable oils, such as sunflower oil, wheat germ oil, olive oil, nuts, seeds, and green vegetables. Tocotrienols are found in palm and rice bran oils and in smaller amounts in some grains and nuts.

Vitamin E helps maintain the integrity of cell membranes and provides stability crucial for the function of cells throughout the musculoskeletal system. It includes bones, joints, and muscles. The antioxidant properties of these molecules contribute to its anti-inflammatory effects. It helps modulate inflammatory processes by reducing the production of pro-inflammatory molecules. Vitamin E mitigates inflammation associated with various musculoskeletal conditions, including arthritis. (Chai SC et al., 2013)

Muscles are a critical component of the musculoskeletal system. Oxidative stress can contribute to muscle damage. Vitamin E’s antioxidant properties help protect muscle cells, contributing to muscle health. Oxidative stress can affect bone remodeling processing and maintain cellular integrity, which is crucial for bone health.

Vitamin B6 (Pyridoxine)

This is one of the B-complex vitamins. It is water-soluble and is obtained through the diet. The body does not store the vitamin in large amounts. Vitamin B6 is essential for metabolizing amino acids, which are the building blocks of proteins. It facilitates the conversion of one amino acid to another. (Hellman H et al., 2010)

Proteins are integral to the structure and function of muscles, connective tissues, and other components of the musculoskeletal system. The vitamin supports the synthesis of proteins and plays an essential role in muscle growth, repair, and overall tissue health.

Vitamin B6 synthesizes neurotransmitters, including serotonin, dopamine, and gamma-aminobutyric acid (GABA). Vitamin B6 helps in the conversion of the amino acid tryptophan into serotonin. Serotonin is a neurotransmitter associated with mood regulation, sleep, and appetite. Adequate levels of vitamin B6 are important for maintaining optimal serotonin synthesis, contributing to emotional well-being.

Proper neurotransmitter synthesis is essential for the communication between nerve cells and is relevant to muscle function and coordination. Vitamin B6 converts amino acid tyrosine to levodopa (L-DOPA). Dopamine is a neurotransmitter involved in various functions, including motivation, pleasure, and movement.

The vitamin also helps in the synthesis of GABA from glutamate. GABA is the main inhibitory neurotransmitter in the central nervous system. It helps calm the nervous system and reduce anxiety.

Adequate oxygen delivery to muscles is crucial for their proper functioning. Vitamin B6 contributes to the synthesis of hemoglobin, supporting oxygen transport to tissues. Glycogen is a storage form of energy in muscles, and its breakdown provides readily available energy during physical activity. Vitamin B6 is involved in the breakdown of glycogen into glucose.

A well-functioning immune system helps prevent infections. Vitamin B6 plays a role in the production of immune cells and antibodies. The dietary sources for this vitamin are whole grains, meat, especially poultry and fish, legumes, nuts and seeds, fortified cereals, and fruits like bananas and avocados.

Vitamin B12

Vitamin B12, also known as cobalamin, is a water-soluble vitamin unique among the B vitamins because it contains cobalt. The vitamin is involved in DNA synthesis, red blood cell formation, and neurological function.

Cobalt is an integral component of vitamin B12. Its deficiency can lead to a pernicious and fatal form of anemia. Vitamin B12 is necessary for the maturation of red blood cells. The vitamin is a cofactor and participates in the conversion of homocysteine to methionine. Elevated levels of homocysteine are associated with an increased risk of cardiovascular disease.

Red blood cells transport oxygen to tissues, including muscles and bones. Vitamin B12 is crucial to normal red blood cell functioning. It is involved in various metabolic pathways, including the breakdown of fatty and amino acids. It contributes to the production of energy essential for muscle function.

Atrophic gastritis and Helicobacter pylori infection (common in developing countries) are common causes of vitamin B12 deficiency. Absolute vegetarianism for an extended period of 5 to 10 years can also lead to a deficiency in this vitamin. Vitamins are only available from foods of animal origin.

This vitamin is essential for synthesizing DNA. Proper DNA synthesis is fundamental for the growth, development, and maintenance of all cells, including those in the musculoskeletal systems.

The vitamin is involved in synthesizing myelin, which forms the protective sheath around nerve fibers. This makes this vitamin essential for the normal functioning of the nervous system. Its deficiency can lead to neurological symptoms, including tingling or numbness of extremities, muscle weakness, and difficulty with balance and coordination.

Animal products are the primary sources of vitamin B12. It includes meat, fish, poultry, eggs, and dairy products. The risk of vitamin B12 deficiency in certain dietary groups, such as vegetarians, is well-recognized. The vitamin is nontoxic, and even high doses do not cause adverse effects. However, cobalt is acutely toxic in larger doses. Fortified cereals with vitamin B12 supplements are now available in retail stores and should be a relief to vegans.

Proteins

Humans require dietary protein, which can be split into two categories: the first is composed of nutritionally indispensable amino acids like histidine, isoleucine, leucine, and lysine. The second component contains nutritionally dispensable amino acids like aspartic acid, asparagine, glutamic acid, alanine, and serine.

A combination of plant-protein foods can serve as a complete and well-balanced source of amino acids essential for all our physiological requirements for this class of molecules.

Some protein sources, like soybeans, are low in sulfur-containing amino acids. Cottonseed, peanuts, sesame flour, and cereal grains are good protein sources but lack lysine. Diet, therefore, is best not restricted to a single protein source (Young et al., 1994).

Nutrients get denatured by heat, changes in pH, detergents, organic solvents, urea, and other chemicals. In heat treatment of soy flakes (while it inactivates nearly all biologically active components), the protein contained therein retains most of its functionality (Wu et al., 1974).

The musculoskeletal system relies on proteins and constituent amino acids for structural support, growth, repair, and overall function.  Let us review proteins and amino acids critical for musculoskeletal health.

Collagen

Collagen is the most abundant protein in the body. It is a major component of connective tissues, including tendons, ligaments, and the extracellular matrix of bones. Collagen also provides support and elasticity to the skin, giving it structure and appearance. It also provides support to muscles and helps transmit force during muscle contractions.  It provides strength and flexibility to these tissues. Blood vessel walls contain collagen. Its role is to provide them with structural support, contributing to the integrity of arteries, veins, and capillaries.

Three main types of collagen are found in the body;

Collagen Type I is found in tendons, ligaments, skin, and bone. It provides a scaffold for depositing minerals like calcium and phosphate, contributing to bone strength and density.

Collagen Type II is found in cartilage and forms a mesh-like network, providing structural integrity and elasticity.

Collagen Type III is present in reticular fibers and is often associated with Type I collagen.

Collagen is involved in the early stages of wound healing, forming a temporary matrix for cell migration and tissue repair. The protein contributes to the structural integrity of various organs and tissues in the body.

Adequate collagen production and maintenance are crucial to the health and integrity of the musculoskeletal system throughout life.  The basic structure of collagen contains the following components:

Glycine, proline, and hydroxyproline are the major amino acids in collagen. Glycine is the most abundant amino acid crucial for its triple-helix structure. Proline and hydroxyproline contribute to the stability of collagen fibers. Lysine and other amino acids facilitate cross-linking between collagen molecules, enhancing the strength of collagen fibers.

Elastin

Elastin protein provides elasticity to various structures in the body. It is a component of connective tissues. Glycine, proline, valine, and alanine are the primary amino acids of this protein. Desmosine and isodesmosine are unique amino acids that form cross-links between elastin molecules, contributing to their elastic properties.

Tropoelastin is the precursor protein to elastin. It is a soluble form of elastin synthesized by cells. It then undergoes maturation and cross-linking to form elastic fibers of elastin.

Elastin is present in tendons and ligaments. In tendons and ligaments, elastin allows for stretching and recoiling during joint movements. In blood vessels, it enables them to stretch and recoil with each heartbeat, helping maintain consistent blood flow. The skin elastin present in the extracellular matrix of the skin helps prevent sagging and maintain skin tone. Elastin fibers in the lung tissue enable the lung to expand during inhalation and recoil during exhalation, facilitating efficient breathing.

Elastin contributes to the elasticity of joint capsules and connective tissue surrounding joints. It allows for movement and flexibility in the musculoskeletal system. It supports activities like bending, stretching, and twisting.

Elastin and collagen provide structural integrity to various tissues. The balance between elastin and collagen fibers determines the mechanical properties of tissues, ensuring appropriate support and flexibility. Similarly, elastin in the ligaments and discs of the spin helps in movements like bending and twisting, supporting the spinal column. It contributes to the flexibility and shock-absorbing properties of the spine.

Myosin and actin

Myosin and actin proteins are involved in muscle contraction. They form the basis of sarcomeres, the structural units of muscle fibers. The interaction between myosin and actin is essential for muscle movement.

Myosin is a motor protein in muscle tissue, particularly muscle fibers. Lysine, arginine, and histidine are its constituent amino acids. Actin is a globular protein. Along with myosin, it forms the contractile apparatus in muscle cells. Its primary amino acids are aspartic acid, glutamic acid, and lysine. Actin molecules are involved in the sliding filament theory of muscle contraction.

Myosin is a key player in muscle contraction, interacting with actin to generate force and movement. Myosin uses energy from ATP hydrolysis to move along actin filaments, leading to muscle contraction. Actin is the major component of thin filaments in muscle cells. It interacts with myosin during muscle contraction.

Osteocalcin

Osteoblasts, cells responsible for bone formation, produce this protein. It regulates bone mineralization and affects glucose metabolism.  Osteocalcin is also known as bone gamma-carboxyglutamic acid (BGLAP). Gamma-carboxyglutamic acid (GLa) residues are the amino acids in the protein.

Osteocalcin regulates calcium and phosphate metabolism within bone tissue. It is involved in the binding and regulating these minerals during the mineralization process. Osteocalcin is a bone formation marker, and its blood or urine levels are measured to assess bone turnover and the rate of new bone formation.

Osteocalcin promotes the deposition of calcium and hydroxyapatite crystals within the bone matrix. Gla residues in osteocalcin bind calcium ions, essential for its biological activity. The activity of this protein is dependent on Vitamin K and Vitamin D.

Glutamine

Glutamine is an amino acid that plays a role in protein synthesis and is a major fuel source for certain cells, including those in the immune system. It supports overall cellular health within the musculoskeletal system. Unlike collagen and elastin, the function of this amino acid is more metabolic and supportive.

Glutamine contributes to muscle protein synthesis, supporting the growth and maintenance of muscle tissue. Muscles use glutamine as an energy source during high-demand or stress periods. The amino acid helps detoxify ammonia, a byproduct of protein metabolism.

Glutamine is essential for immune cell functioning and supports immune response during periods of stress or injury. It has potential anti-inflammatory effects. In conditions with muscle mass loss, such as during illness or injury, glutamine helps prevent muscle wasting. It contributes to collagen synthesis. The body can produce the amino acids. During periods of intense physical activity, stress, illness, or injury, dietary or supplemental glutamine supports to meet increased metabolic demands of the musculoskeletal system.

Branched-chain amino Acids (BCAAs)

BCCAs are essential amino acids in muscle protein synthesis. They are obtained through diet or supplementation. They are important for muscle growth, repair, and maintenance. Its constituent amino acids are leucine, isoleucine, and valine.

Leucine initiates muscle protein synthesis and stimulates the synthesis of new proteins, including those involved in muscle building and repair. BCAAs serve as an energy source for muscles during exercise or periods of increased energy demand. They can be broken down and used as fuel, particularly during endurance activities when the body’s carbohydrate stores are depleted.

These amino acids help reduce muscle soreness and damage following intense exercise. They also help prevent or alleviate delayed-onset muscle soreness. They further prevent muscle tissue breakdown, especially during calorie restriction, fasting, or other stress. Leucine has been seen to improve insulin sensitivity, support metabolic health, maintain a positive protein balance, and improve overall musculoskeletal health. Isoleucine serves as a precursor for other amino acids involved in collagen synthesis.

BCAAs are found in meat, dairy, and other protein-rich plant-based foods.

Proline, glycine, and lysine

These amino acids are crucial for collagen synthesis, contributing to the formation and stability of collagen structures. Collagen with proline as a structural component strengthens and supports tendons, ligaments, skin, and other connective tissues. Glycine is the smallest amino acid and is highly abundant in collagen. It supports the integrity of connective tissues, promoting their strength and flexibility. Lysine, too, is involved in synthesizing proteins that contribute to bone health. It plays a role in the absorption of calcium.

A deficiency of these amino acids weakens collagen fibers, compromising the integrity of connective tissues, contributing to joint laxity, and increasing susceptibility to injuries. Proline and glycine are constituents of collagen Type II, which is responsible for maintaining cartilage health. 

Lysine is essential for bone matrix protein synthesis. Deficiencies of this amino acid weaken bones and increase the risk of fractures. They also cause delayed healing of damaged tissues, impair joint function, and affect range of motion.

Herbs and botanicals

Treatment of chronic joint inflammation and oxidative stress in osteoarthritis and rheumatoid arthritis is often supported with herb and botanical extracts, combinations, and extracts. These herbs have been traditionally used over the millennia to relieve such patients. A preference for herbs and botanical products is emerging as a promising alternative because of a lower rate of adverse events and efficiency that is frequently comparable to conventional drugs.

Some of the herbs traditionally used are Arnica montana, Boswellia spp, Curcuma longa, Equisetum arvense, Harpagophytum procumbens, Salix spp, Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Withania somnifera. These herbs have been proven effective in studies done in vitro or on animal models. (Dragos D et al., 2017)

Still, botanical supplements are not getting mainstreamed into disease management because of the following reasons:

1. Human clinical evidence is scarce for many of these herbs.
2. Herbal products can vary widely in composition, and their quality is not always standardized.
3. Lack of regulation and quality control measures result in variability in the concentration of active compounds, affecting the reliability and consistency of outcomes.
4. The bioavailability of active compounds in herbs and botanicals can be variable. These suffer from poor absorption, metabolism, and rapid elimination, limiting the effectiveness of compounds and leading to challenges in achieving therapeutic levels in the body.
5. Several herbs and botanicals are traditionally used to reduce inflammation and alleviate arthritis symptoms. We have briefly reviewed turmeric and ginger in the last chapter.
6. Herb-drug interactions pose a significant concern. Certain herbs may interfere with drug metabolism, affecting efficacy and increasing the risk of adverse events.
7. Herbal formulations vary. Individuals respond differently to herbal remedies, and some work effectively in one person but not in another, making it challenging to predict individual responses.
8. Unlike pharmaceutical medications, herbal remedies are often slower to act. This can be a constraint for individuals seeking immediate relief from pain or inflammation.
9. Lack of standardized labeling, inconsistent product quality, and potential contamination issues pose challenges for healthcare professionals and consumers.
10. Demand for herbal products often results in overharvesting and environmental degradation. Sustainable and ethical sourcing practices are important for preserving biodiversity and ensuring the long-term availability of herbal remedies.

Let us look at a couple of botanicals to understand the effectiveness of these supplements.

Boswellia (Boswellia serrata)

Boswellia serrata, common name Indian frankincense, is a mid-sized tree growing in dry parts of India, the Middle East, and Africa. The resin from the tree is used in Ayurvedic medicine. The resin and sap are traditionally used as anti-inflammatory medicines. Boswellic acids present in the plant are bioactive compounds that inhibit the activity of inflammatory mediator enzymes. The supplements are used for their analgesic properties, improving joint function and mobility in osteoarthritis patients. (Siddiqui MZ, 2011, Umar S et al., 2014).

A twelve-week clinical trial in which a combination of extracts from Boswellia serrata and curcumin derived from turmeric was seen to act synergistically and was found to be more effective in reducing pain symptoms in osteoarthritis patients. (Haroyan A et al., 2018). Another group of scientists also recommends the therapeutic use of Boswellia serrata extracts for providing pain relief to osteoarthritis patients. (Kimmatkar N et al., 2003)

Devil’s Claw

Harpagophytum procumbens is another plant traditionally used for joint pain and inflammation in osteoarthritis. Harpagoside is a key compound with anti-inflammatory properties. A review of multiple studies indicates that Harpagophytum powder effectively treats spine, hip, and knee osteoarthritis. (Gagnier JJ et al., 2004)

Willow bark (Salix spp)

Salicin is the inflammatory and analgesic compound found in the bark of the willow tree. The compound is converted into salicylic acid in the body and has been seen to provide relief similar to aspirin. The compound is a complementary supplement for pain relief in conditions like osteoarthritis. (Setty AR et al., 2005)

Supplements

Nutritional and other supplements are used extensively for musculoskeletal system conditions.

Supplement	Role	Use
Calcium	Bone health and density	Osteoporosis
Collagen	Structural support to the connective tissues, including joints, tendons, and ligaments	Joint health, arthritis.
Glucosamine	Repair of joint tissues	Osteoarthritis
Omega-3 fatty acids	Anti-inflammatory properties, joint health	Arthritis, joint pain
Vitamin D	Calcium absorption and bone health	Osteoporosis, bone health
Vitamin K	Bone mineralization	Osteoporosis, bone health.
Curcumin	Anti-inflammatory and antioxidant	Osteoarthritis, joint pain.
Boswellia serrata	Anti-inflammatory	Osteoarthritis, joint inflammation.
Methylsulfonylmethane (MSM)	Joint health	Arthritis, joint pain.
Chondroitin	Joint structures, cartilage	Osteoarthritis
Zinc	Immune function	Bone health and immune support.
Magnesium	Hone health and muscle function	Bone health and muscle function.
Probiotics	Gut health and systemic inflammation	General health.
Vitamin C	Collagen synthesis and antioxidant	Collagen formation and immune support.
Vitamin E	Antioxidant	Anti-inflammatory support.
Ginger extract	Anti-inflammatory and analgesic	Joint pain, arthritis
S-Adenosylemethoione (SAMe)	Cartilage production	Osteoarthritis
Tart Cherry Extract	Anti-inflammation	Joint pain, gout.
Vitamin B6	Nerve health	Neuropathic pain, general health.
Arnica	Anti-inflammation	Bruises, sprains, and muscle soreness.

 

Conclusion

Nutritional supplements play a crucial role in supporting the health of the musculoskeletal system. They provide essential nutrients for bone, joint, and connective tissue function. Key nutrients such as calcium, vitamin D, and vitamin K are vital for bone health. These support bone mineralization and density. The supplements are recommended to prevent osteoporosis and maintain a strong skeletal structure.

Collagen supplements provide structural support to connective tissues, including joints, tendons, and ligaments. Glucosamine and chondroitin are components of cartilage and are commonly used to support joint health conditions like osteoarthritis. Omega-3 fatty acids are known for their anti-inflammatory properties and are recommended for managing arthritis and reducing joint pain.

Additionally, antioxidants such as vitamins C and E help protect tissues from oxidative stress, potentially alleviating inflammation. Herbal supplements like turmeric and Boswellia serrata are known for their anti-inflammatory properties and are used to support musculoskeletal health, particularly in managing conditions associated with inflammation.

 

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