Osteoarthritis, the most common form of arthritis, affects approximately 12 per cent of adults (21 million people) in the United States.1 In Great Britain, about six per cent of adults (2.6 million) have frequent knee pain and X-ray evidence of osteoarthritis; this number increases to 12 per cent (5.2 million) among people over age 65.2 The disease is characterized by a thinning of the cartilage pads in the knees and, less frequently, at other joints. Symptoms include pain, stiffness, inflammation and a lack of physical mobility.
Two nutritional approaches, or a combination of them, offer many benefits to people with osteoarthritis. As such, they provide a conceptual framework for formulating dietary supplements.
One approach focuses on nutritional compounds that enhance the structure of articular (joint) cartilage, which provides both cushioning and lubrication at joints. The rationale is that the body's physical structure and biochemistry ultimately depend on nutrition. Nutritional precursors to cartilage can help the body maintain and sometimes stimulate the regeneration of articular cartilage.
The other approach reduces inflammation to control pain and limit the breakdown of cartilage. Inflammation is part of the body's natural mechanism to remove dead or damaged chondrocytes, the body's cartilage-making cells. However, chronic inflammation leads to the breakdown of cartilage, and it can result from an imbalance in the body's pro- and anti-inflammatory compounds, such as prostaglandins and leuko-trienes. Once again, these substances depend on nutritional precursors.
Supporting cartilage structure
Eighty per cent of articular cartilage consists of water, which provides much of the cushioning effect of the tissue's cushioning properties. The remaining 20 per cent consists of both collagen and noncollagen proteins. The outer regions of cartilage have greater resiliency, whereas cartilage becomes more mineralised and denser close to bone.
Collagen type 2 cartilage provides 90-98 per cent of the collagen protein, with the remainder consisting of type 5, 6, 9, 10 and 11 collagens. In contrast, the noncollagen proteins have a complicated 'Russian doll' structure. To explain, proteoglycans form the main type of noncollagen protein, and aggrecan is the predominant type of proteoglycan. Proteoglycans consist of several types of glycosaminoglycans, including chondroitin sulphate, hyaluronic acid, keratan sulphates 1 and 2, and heparin sulphate.
Sulphur is one of the common denominators in many supplements —?including glucosamine sulphate, chondroitin sulphate, and methylsulfonylmethane (MSM) — that have been shown to enhance the structure of articular cartilage and reduce pain. In fact, glycosaminoglycan production depends on the presence of sulphur, and one study found that glucosamine sulphate supplements increased blood levels of sulphur, but not glucosamine.3 Although sulphur is not recognised as an essential dietary mineral, it is the third most abundant mineral in the body (after calcium and phosphorus). Its functionality may be related to the organic molecule to which it is attached.4
Glucosamine may not be the newest ingredient in joint health, but it does work. More than 40 clinical trials have found that glucosamine sulphate supplements can reduce pain, and two studies reported X-ray evidence showing the growth of new articular cartilage.5 In a recent study, published in Osteoarthritis and Cartilage, researchers followed patients in earlier clinical trials who had taken either glucosamine sulphate or placebos daily for one to three years. People who had taken glucosamine sulphate were half as likely (compared with those who had taken placebos) to undergo total knee-replacement surgery over the subsequent eight years.6
The controversial Gluosamine/Chondroitin Arthritis Intervention Trial (GAIT) was widely reported as showing no benefits for glucosamine hydrochloride. However, the combination of glucosamine and chondroitin sulphate together brought substantial pain relief to patients with the most severe symptoms. The combination worked better than either supplement by itself or the pharmaceutical drug celecoxib.7
Chondroitin sulphate is a structural component of cartilage. Considerable clinical research has also shown that it reduces pain and helps maintain articular cartilage.8 A meta-analysis published in Current Medical Research and Opinion found that chondroitin provided significant clinical benefits to patients with osteoarthritis. One of the studies showed that chondroitin sulphate supplements led to a reduced need for analgesic medications.9
Methylsulfonylmethane (MSM) is chemically related to dimethyl sulfoxide (DMSO), which has a long history of use as a topical analgesic in veterinary and alternative medicine. Taken orally, MSM has been found to reduce pain in people with osteoarthritis. One study reported significant improvements with 3g/day MSM taken for 12 weeks.10 Taking 1,500mg/day MSM in combination with 1,500mg/day glucosamine sulphate was more effective in reducing pain and swelling and in improving the functional ability of joints than the individual agents.11
Hyaluronic acid is a constituent of joints. Intra-cartilage injections of hyaluronic acid are occasionally used to treat osteoarthritis, but many experts have questioned whether it can be absorbed orally. In a study published in Nutrition Journal, researchers reported that 80mg/day oral hyaluronic acid significantly lessened pain and improved mobility. The hyaluronic acid was derived from chicken combs.12
Type 2 collagen is the predominant type of collagen protein (as opposed to noncollagen protein) in joints. Intuitively, oral supplements would benefit people with osteoarthritis by providing some of the biochemical building blocks of cartilage. In laboratory studies, type 2 collagen stimulates the synthesis of chondrocytes,13 and a small study found that supplements of type 2 collagen did lead to less pain and greater mobility in patients.14 However, the benefits of type 2 collagen appear greater in patients with rheumatoid arthritis.15,16
Pycnogenol is a proprietary extract of French maritime pine trees that is the beneficiary of research on anti-inflammation properties, joints and much more. It is a rich trove of antioxidant and anti-inflammatory polyphenols. It blunts the activity of inflammation-promoting COX-1 and COX-2 enzymes.17 In a recent study, Pycnogenol supplements reduced pain and stiffness in people with osteoarthritis.18 In another study, this one focusing on asthma, children taking Pycnogenol gained better lung function, and many were able to reduce or stop using their medications.19
Quelling inflammation in osteoarthritis
Given the appropriate dietary building blocks, the body can manufacture a variety of pro- and anti-inflammatory compounds. Many of these compounds, such as prostaglandins and leukotrienes, are downstream products of essential fatty acids. In addition, antioxidants modulate the inflammatory response, such as by diminishing the activity of adhesion molecules. Many nutrients support the body's systemic ability to control inflammation, and some have documented benefits in osteoarthritis.
The omega-6 and omega-3 ratio is a powerful determinant of the body's ability to regulate inflammation. As a general (though not completely accurate) rule, omega-6 fatty acids are considered pro-inflammatory, whereas omega-3 fatty acids are considered anti-inflammatory.
Traditionally, the omega-6:omega-3 dietary ratio has been approximately 1:1. With the widespread consumption of processed foods and oils (particularly corn, safflower, peanut and soybean oils), this ratio is now approximately 20:1, favouring the omega-6s and resulting in a predisposition toward greater inflammation. This change has been further amplified by the widespread consumption of trans fats, which inhibit some of the enzymes in the fatty acid pathways.20,21
Omega-3 fatty acids lead to the production of prostaglandin E3 and leuko-triene B5, both of which are anti-inflammatory. Cell studies have found that the omega-3s inhibit the activity of aggrecanases, the enzymes that break down aggrecan (the principal noncollagen protein in cartilage).22 In one study, using cultured cells from the knees of osteoarthritis patients, researchers confirmed that the omega-3 fatty acids reduced cyclo-oxygenase-2 (COX-2) enzyme activity and blocked the breakdown of chondrocytes.23
Gamma-linolenic acid (GLA) is an omega-6 PUFA, yet it has significant anti-inflammatory properties. Under normal circumstances, GLA is rapidly converted to dihomo-GLA, which can enter two pathways. In one, it quickly converts to prostaglandin E1, which is anti-inflammatory. In the other, dihomo-GLA converts to arachidonic acid, which is pro-inflammatory.
Elevated insulin levels (characteristic of insulin resistance, prediabetes, diabetes and abdominal obesity) increase the conversion of dihomo-GLA to arachidonic acid, which ultimately leads to pro-inflammatory prostaglandin E2 and leukotriene B4. Studies have found GLA supplements helpful in reducing inflammation stemming from athletic injuries and rheumatoid arthritis,24,25 and they may have general benefits in osteoarthritis.
Trans fats interfere with the production of GLA by inhibiting the delta-6-desaturase enzyme. GLA specifically leapfrogs the delta-6-desaturase enzyme.
Curcumin is an extract of the herb turmeric with broad anti-inflammatory benefits. Although curcumin's role in osteoarthritis research is limited, researchers do have a clear understanding of how this nutritional ingredient works. Curcumin reduces inflammation through 97 different biochemical pathways, which are listed in a detailed review in Biochemical Pharmacology.26 It blocks the activity of nuclear factor kappa beta (NF-kappaB, a gene transcription factor), interleukin-6 (a cytokine), and COX-2 (a pro-inflammatory enzyme). In addition, recent cell and animal experiments have found that curcumin enhances the effects of pharmaceutical analgesics.27
Rose hips were popular in the 1970s. Although a source of 15 pro-anthocyandins, they have largely receded in the supplement marketplace.28 A meta-analysis of three studies, published in Osteoarthritis and Cartilage in 2008, found that 5g/day rose hips led to substantial decreases in pain (twice that of the placebo groups) in more than 300 patients with osteoarthritis.29
Avocado / Soybean unsaponifiables (ASU) is an extract of avocado and soybean. It has been shown to reduce pain, slow the breakdown of cartilage and stimulate the synthesis of new cartilage.30,31,32 A recent Danish review of four published studies found that ASU reduced pain in people with knee osteoarthritis.33 Another study reported that a combination of ASU, glucosamine and chondroitin sulphate reduced the activity of genes involved in making interleukin-6 and tumour necrosis factor, both promoters of inflammation.34,35
Astaxanthin inhibits NF-kappaB, which would otherwise stimulate the expression of inflammation-promoting genes.36 Cell and animal studies have documented the anti-inflammatory benefits of this antioxidant carotenoid. It also blocks other inflammation promoters, including tumour necrosis factor alpha, interleukin-1B, COX-1 and COX-2 enzymes, and prostaglandin E2.37,38
Boswellia is an herb known more formally as Boswellia serrata, with a long history of medicinal use in Ayurvedic traditions. Its biologically active constituents are known as boswellic acids. Many of boswellia's anti-inflammatory benefits appear related to its ability to inhibit 5-lipoxygenase, an enzyme involved in the production of pro-inflammatory leukotrienes.39,40 This mode of action is different from most natural and pharmaceutical products, which inhibit the activity of COX enzymes.
Because of the research, product formulators have many different options in designing natural and safe products for people with osteoarthritis. They can focus on individual ingredients, or they can use formulas to differentiate their products in the marketplace. Such formulas could focus on preventing and reversing the breakdown of cartilage, or on reducing inflammation —?or both.
Jack Challem is the author of The Food-Mood Solution, and Stop Prediabetes Now, both published by John Wiley & Sons.
Select suppliers: targeting inflammation and joint health
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