Arthritis - Osteoarthritis
Targeted nutritional interventions contain a variety of biologically active compounds known to positively influence cartilage degradation in osteoarthritis (OA). Unlike medications, nutritional interventions don’t typically cause side effects, which may explain why nearly one out of every five OA patients uses alternative methods (Ameye 2006).
Joint Structure Support
Glucosamine – Glucosamine is a component of larger compounds called glycosaminoglycans and proteoglycans, which help trap water in the matrix of cartilage, providing it with the flexibility and resilience it needs to function properly (Sanders 2011). In laboratory models, glucosamine has been shown to possess both anti-inflammatory and disease modifying effects in OA (Aghazadeh-Habashi 2011). In addition, researchers believe that glucosamine may repair cartilage by stimulating synthesis of chondrocytes (Fouladbakhsh 2012). Glucosamine also plays a crucial role in maintaining joint lubrication (Sanders 2011).
Commercial glucosamine preparations consist of either glucosamine hydrochloride or glucosamine sulfate (Miller 2011a). When compared to placebo, high-quality clinical data indicate that glucosamine sulfate is superior for relieving the severity of OA symptoms (Herrero-Beaumont 2007).
Although there remains some controversy in the conventional medical community over the effectiveness of glucosamine for osteoarthritis , most published studies show that glucosamine sulfate is effective and studies that have found otherwise have been limited by methodological flaws and dosing/ formulation inconsistencies (Bijlsma 2011; Aghazadeh-Habashi 2011). Since glucosamine offers promise as structural support in osteoarthritis, additional research is planned (Seed 2011).
Because cartilage takes time to synthesize, and glucosamine is only one of its structural components, experts recommend up to 8 weeks of initial therapy before making an assessment concerning efficacy (Sanders 2011).
Chondroitin – Chondroitin sulfate is a complex sugar molecule found in connective tissue such as bone, cartilage, tendons, ligaments, and skin (Martel-Pelletier 2015). Complexes of chondroitin sulfate in cartilage create a gel-like material and contribute to water retention, lubrication, and resiliency. One study found that cartilage samples from arthritic joints had lower concentrations of chondroitin sulfate than samples from healthy joints (Ishimaru 2014). In laboratory studies, chondroitin sulfate reduced inflammation and promoted a healthy balance between breakdown and new formation of bone and cartilage (Martel-Pelletier 2015; Henrotin 2014). Laboratory studies of cartilage-producing cells suggest chondroitin and glucosamine sulfates may work synergistically to protect cartilage (Calamia 2014).
Randomized controlled clinical trials show 800 mg to 1200 mg per day of chondroitin sulfate can prevent progression of cartilage loss and reduce pain in patients with OA of the knee (Kahan 2009; Wildi 2011; Zegels 2013). Chondroitin sulfate also decreased pain and improved function in patients with OA of the hand (Gabay 2011). A meta-analysis of clinical studies determined chondroitin sulfate is effective for improving measures of pain and functioning with little risk of adverse side effects in patients with OA (Singh 2015). It is worthwhile to note that findings from a meta-analyses show two or more years of daily use may be needed before a beneficial effect on cartilage protection is seen (Lee 2010). Clinical research has demonstrated that treatment of osteoarthritic joints with the combination of glucosamine and chondroitin sulfates can relieve pain, improve function, and enhance joint structure (Hochberg 2016; Raynauld 2016).
Chondroitin sulfate appears to relieve pain more effectively and has a better safety profile than NSAIDs (Henrotin 2014; Hochberg 2013). A randomized controlled trial compared 1200 mg per day of chondroitin sulfate to 200 mg per day of celecoxib (Celebrex) in 138 patients with OA of the knee. After two years of treatment, the two treatment groups experienced similar reductions in swelling and symptoms such as knee pain and stiffness; however, MRI measurements showed that those taking chondroitin sulfate had significantly less cartilage volume loss (Pelletier 2016). In a randomized clinical trial with 605 participants with OA of the knee, a group receiving a combination of 800 mg of chondroitin sulfate plus 1500 mg of glucosamine sulfate daily had less joint space narrowing after two years than groups receiving placebo or either supplement alone (Fransen 2015).
Hyaluronic acid - Hyaluronic acid (HA) is secreted by chondrocytes and used as a basic building block for cartilage synthesis. Researchers believe that HA is useful in the management of OA because it interferes with pain mediators and decreases the production of key enzymes (i.e., metalloproteinases) responsible for digesting and destroying healthy cartilage tissue (Palmieri 2010). Hyaluronic acid intra-articular injections are used to treat OA of the knee. It has been linked to improvements in pain and functional status among OA patients (Iannitti 2011), especially when combined with other treatment strategies (Palmieri 2010).
Hyaluronic acid is typically administered intra-articularly; however, HA is absorbed orally much more efficiently when formulated with a phospholipid (Huang 2007).
Findings from an experimental trial show that orally administered hyaluronic acid improved the prognosis of horses that underwent joint surgery. In a blinded, placebo-controlled experiment involving 48 thoroughbreds, 30 days of post-operative use of oral hyaluronic acid significantly improved outcomes (McIlwraith 1991; Bergin 2006).
In a randomized, placebo-controlled, double-blind study of 20 human patients with OA of the knee, subjects received 80 mg of a specially formulated, orally ingested hyaluronic acid supplement called Hyal-Joint™ or a placebo daily for eight weeks. The treatment group had a greater magnitude of improvement in bodily pain and social functioning (Kalman 2008).
Sulfur Compounds – Sulfur containing compounds, such as Methylsulfonylmethane (MSM), are commonly found in fruits, vegetables, grains, as well as the human body (AMR 2003). Experts believe that these compounds may reduce peripheral pain and inhibit the degenerative changes of OA by stabilizing cell membranes and scavenging free radicals that can lead to inflammation. In clinical trials, MSM was able to reduce both pain and swelling among OA patients. It is well tolerated and not associated with any significant side effects (Gregory 2008). Another study found that patients with OA of the knee taking MSM for 12 weeks demonstrated an improvement in pain and physical function (Debbi 2011).
Keratin is another sulfur-rich compound (Hill 2010) that supports joint health by supplying building blocks for joint repair, stimulating antioxidant enzymes, and acting as an antioxidant itself (Quaglini 2010; Aitken 2010). In a clinical evaluation, supplementation with solubilized keratin relieved OA pain more than placebo (Aitken 2010).
S-Adenosylmethionine - S-Adenosylmethionine (SAMe) is naturally occurring within the body and has been reported to possess both anti-inflammatory and analgesic effects. Clinical trials have shown that SAMe can reduce pain, stiffness, and increase functioning among patients with OA (Hardy 2003; Kim 2009). Moreover, SAMe has been found to be as effective - yet safer – than NSAIDs in the treatment of OA in some populations (Soeken 2002). SAMe may achieve this by stimulating the production of cartilage through one of these potential mechanisms: modulating cellular growth/survival signals within joints, reducing inflammatory mediators, and/or increasing the production of antioxidants like glutathione (Hosea 2008). SAMe is not found in food (Rutjes 2009).
Omega-3 Fatty Acids – Omega-3 fatty acid supplementation is generally recommended for individuals consuming a typical Western diet (high in pro-inflammatory omega-6 fatty acids) (Simopoulos 2006; Knott 2011). Increased levels of omega-6 fatty acids have been linked to the destruction of bone and cartilage among OA patients; supplementation with omega-3 fatty acids can combat this effect (see figure 1) (Knott 2011). Omega-3 fatty acids have also been shown to reduce the amounts of certain proteins that are important in the pathology of OA (Zainal 2009). In the clinical setting, the combination of omega-3 fatty acids with glucosamine was more effective at reducing morning stiffness and pain than glucosamine alone (Gruenwald 2009).
Krill - Krill are cold water, shrimp-like crustaceans that are rich in omega-3 fatty acids (AMR 2010). In OA patients or those with related inflammatory conditions, supplementation with 300 mg of krill oil daily for seven days reduced C-reactive protein (CRP) – a marker of inflammation – by more than 15% compared to placebo. By day 30, the reduction doubled to more than 30%. Additionally, seven days of krill oil treatment reduced pain nearly 30%, stiffness more than 20%, and functional impairment almost 23% (Deutsch 2007).
Undenatured Type-II Collagen – Undenatured Type-II Collagen (UC-II) has received considerable attention as a therapeutic agent in OA (Crowley 2009). Recent discoveries have revealed that gradual destruction of joints in OA leads to the exposure of joint collagen, which triggers an immune response that launches an autoimmune-like inflammatory attack on the joint (Heinegard 2011). UC-II functions as a “switch” to turn off this immune response. It does so by inducing what immunologists call specific oral tolerance—the desensitization of immune response to specific agents via an orally administered intervention (Gupta 2009). Among OA patients, UC-II has been shown to significantly enhance daily activities and is not generally associated with any side effects (Crowley 2009).
Soy and Avocado Oil – Avocado and soy unsaponifiable (ASU) mixtures may stimulate collagen synthesis and promote cartilage repair, as well as reduce circulating levels of pro-inflammatory cytokines, which are implicated in the pathology of OA (Kucharz 2003; Priotta 2010). A review of four clinical studies involving ASU treatments among OA patients found evidence for its use in reducing pain and improving function (Christensen 2008). Among OA patients, ASU also significantly reduces the need to take NSAIDs (Long 2001). ASU mixtures have been recommended by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) for the symptomatic treatment of OA (Henrotin 2008).
Curcumin – Curcumin is a natural plant phenolic compound that has been shown to possess potent anti-inflammatory and antioxidant properties (Singh 2007). Research suggests that curcumin may represent a viable alternative to NSAIDs, and that it may complement the activity of some OA drugs (Henrotin 2010; Lev-Ari 2006). Curcumin’s effectiveness in OA may be due to its ability to attenuate nuclear factor kappa B (Nf-kB) signaling, reduce the production of inflammatory mediators (Mathy-Hartert 2009; Henrotin 2010), and interfere with cartilage destruction (Mathy-Hartert 2009). Curcumin has been recommended for the long-term complementary management of OA (Belcaro 2010a; Belcaro 2010b).
Ginger – Zingiber officinale (i.e., ginger) is related to curcumin. It has traditionally been used for a wide variety of medicinal purposes due to its antioxidant, antimicrobial, and anti-inflammatory properties (Butt 2011). Evidence suggests that ginger supplementation may reduce the subjective experience of pain, especially with respect to OA (Terry 2011). Clinical research has demonstrated that oral ginger extract can improve OA symptoms, and may be as effective as ibuprofen (Haghighi 2005). Interestingly, when applied topically in the form of a warm compress, ginger promotes relaxation and analgesia (Therkleson 2010).
Boswellia - Boswellia serrata is a tree commonly found in the hilly areas of India (Clayton 2007). In the last two decades, the use of gum resins extracted from this tree has become popular among Western cultures (Abdel-Tawab 2011). This is because it is reported to possess beneficial anti-inflammatory, anti-arthritic, and analgesic properties (Clayton 2007). Specifically, compounds in boswellia such as 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) are inhibitors of the inflammatory enzyme 5-lipoxygenase (5-LOX) (Siddiqui 2011).
One of the first high-quality clinical studies involving the use of Boswellia serrata extract for the treatment of OA of the knee found that it was associated with a reduction in pain and swelling, as well as an improvement in function and range of movement. In addition, Boswellia serrata extract was well tolerated, and thus recommended for patients with OA of the knee (Kimmatkar 2003). Boswellia serrata extract has not only been shown to be clinically efficacious for reducing the symptoms of OA (e.g., pain and function), but also appears to be able to fortify cartilage against damage and promote its repair (Sengupta 2010; Sengupta 2011).
Korean Angelica - Decursinol is a medicinal compound found in the roots of the Korean flower Angelica gigas Nakai (Korean angelica) (Song 2011). It has been widely utilized in traditional Asian medicine as a treatment for pain associated with various conditions (e.g., arthritis) (Kim 2009). Laboratory evidence shows that an active constituent derived from Korean Angelica inhibits activation of nuclear factor-kappa B (Nf-kB) (Kim 2006). Decursinol may also act within the central nervous system to relieve pain (Choi 2003). One study found that co-administration of decursinol and acetaminophen resulted in synergistic pain-relieving effects. The authors of this study attributed the analgesic effect of decursinol to its ability to reduce the activity of the pro-inflammatory enzyme cyclooxygenase (Seo 2009).
Proteolytic enzymes – Numerous clinical studies have evaluated the efficacy of various preparations of proteolytic enzymes for conditions ranging from rheumatoid arthritis and muscular pain, to kidney disease and chronic airway disorders (Nakamura 2003; Ritz 2009). In one trial among 80 patients with OA of the knee, proteolytic enzymes were found to be as effective as the NSAID diclofenac for relieving pain and improving function (Singer 1996). Some early trials indicate that the proteolytic enzyme bromelain may be effective for relieving OA pain (Brien 2004).
One study reported that a supplement containing bromelain (90 mg, three times daily) was as effective as diclofenac (50 mg, twice daily) in improving the symptoms of osteoarthritis of the knee. Patients reported comparable reductions in joint tenderness, pain and swelling, and improvement in range of motion at the end of the study. The investigators found bromelain to be as good as diclofenac on a standard pain assessment scale and to be better than the drug in reducing pain at rest (by 41% for bromelain versus 23% for the drug), improving restricted function (by 10% for bromelain versus 0% for the drug), being rated by more patients in improving symptoms (24% for bromelain versus 19% for the drug), and being evaluated by more physicians as having good efficacy (51% for bromelain versus 37% for the drug). In summary, the investigators determined bromelain to be an effective and safe alternative to NSAIDs such as diclofenac for painful osteoarthritis (Akhtar 2004).
Experts generally advise consuming enteric-coated bromelain supplements to benefit from its anti-inflammatory effects.
Vitamin D - Vitamin D is a prohormone version of an important hormone called 1,25-dihydroxycholecalciferol or 1,25-dihydroxy vitamin D, also known as calcitriol (Dusso 2005). Vitamin D, once converted into calcitriol, inhibits inflammation by regulating some of the genes responsible for producing pro-inflammatory mediators (i.e., cytokines) (Manson 2010). Evidence suggests that patients with osteoarthritis have lower blood levels of vitamin D than healthy controls (Muraki 2011); this was especially true of younger osteoarthritis patients (i.e., <60) in one study (Heidari 2011).
Life Extension recommends routine vitamin D deficiency testing for all individuals with pain complaints. If vitamin D levels are low, vitamin D supplementation may result in significant improvements in pain (Selfridge 2010). Life Extension suggests that blood levels of 25-hydroxyvitamin D should be kept between 50 and 80 ng/mL for optimal health.
Oxidative stress is involved in OA-associated inflammation and pain (Ziskoven 2011). Researchers have found that damaged human chondrocytes release free-radicals, which can exacerbate joint destruction (Rosenbaum 2010). Therefore, OA patients should maintain an adequate intake of antioxidants such as astaxanthin and vitamin C (Nakao 2010; Breidenassel 2011); especially since antioxidant-deficient diets may increase the risk of OA (Rosenbaum 2010).
Green Tea Extracts – Epigallocatechin gallate (EGCG), the major and most biologically active component of green tea, was shown in an in vitro study to protect human chondrocytes from inflammatory damage (Akhtar 2011). This may be due to EGCG’s ability to inhibit the expression of inflammatory mediators (e.g., COX-2 and nitric oxide) (Rosenbaum 2010). However, EGCG is only one of several green tea polyphenols (GTPs). A GTP mix has shown promise for managing symptomatic OA. An expert review on green tea’s role in OA theorizes that GTP mixtures may be beneficial when used in combination with traditional OA treatments (Katiyar 2011).
The following list of additional treatment options may be useful for managing the symptoms of OA.
- Acupuncture – Among OA patients, acupuncture is able to decrease pain levels and increase quality of life estimates. Experts believe that acupuncture achieves its analgesic effect by stimulating the body’s natural opioid system and reducing the release of stress hormones (Sanders 2011).
- Boron - Boron is an essential nutrient for healthy bones and joints. Evidence suggests that it is safe and effective for the treatment of OA (Newnham 1994).
- Niacinamide – Niacinamide, a form of vitamin B3, has been shown to reduce inflammation, decrease consumption of anti-inflammatory medications, and increase joint mobility in OA patients (Jonas 1996). One hypothesis suggests that it may have achieved these effects by modulating inflammatory pathways of joint destruction (McCarty 1999).
- Mineral Complex – In a clinical study among OA patients, aquamin F (a seaweed-derived mineral mixture) was associated with an increased range of motion and walking distance. Its use in OA may also result in a decreased need for NSAIDs (Frestedt 2009). Most high quality multivitamins contain adequate concentrations of minerals.
- Mitochondrial Support – Resveratrol, and theoretically other nutrients that support mitochondrial health like coenzyme Q10 (CoQ10) and pyrroloquinoline quinone (PQQ), may be able to ease inflammation and oxidative stress in chondrocytes. Mitochondrial dysfunction can increase inflammation in these cells, potentially impairing cartilage and joint function in OA (Vaamonde-Garcia 2012).
- Topical olive oil – In 2012, a four-week long clinical trial compared topical virgin olive oil to topical piroxicam, an NSAID, among thirty women aged 40 – 85 with osteoarthritis of the knee. From week two through four, those randomized to the olive oil treatment reported less pain and greater physical function than those using piroxicam (Bohlooli 2012).
- Gamma linolenic acid - GLA, a plant-derived omega-6 fatty acid, plays an important role in modulating inflammation throughout the body, especially when incorporated into the membranes of immune system cells (Johnson 1997; Ziboh 2004). It was noted that GLA regulates the inflammatory "master molecule" nuclear factor-kappa B (Nf-kB), preventing it from switching on genes for inflammatory cytokines in cell nuclei (Chang 2010). While GLA has been shown to be effective among rheumatoid arthritis patients (Soeken 2004), more research is needed to determine its effectiveness in OA.
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