Arthritis – Osteoarthritis


Osteoarthritis is a very common degenerative joint disease and a leading cause of disability. Affecting over 20 million in the U.S. alone, this progressive disease is characterised by structural damage and functional impairment within joints (CDC 2012; NIH Medline Plus 2012; Mayo Clinic 2012; Seed 2011; Lawrence 2008; Lane 2011).

Many interrelated factors – such as obesity and oxidative stress – work together in osteoarthritis to cause progressive, degenerative changes in weight-bearing joints including the knees, neck, lumbar spine, and hips, as well as the hands. A multifactorial approach is best when targeting osteoarthritis management (Ziskoven 2011; Busija 2010).

Conventional medical treatment focuses upon reducing load (e.g. weight loss) and improving joint support (i.e. enhancing muscle strength), as well as treating the pain and stiffness of osteoarthritis with acetaminophen and other NSAID drugs.

However, these drugs expose arthritis sufferers to the risks of liver and kidney damage (Woodcock 2009). In addition, these drugs often offer only incomplete/ partial relief (Vista 2011; Bijlsma 2011), and treatment with acetaminophen and NSAIDs fails to help the body rebuild damaged joint cartilage (Kapoor 2011).

On the other hand, natural compounds like undenatured type-II collagen and methylsulfonylmethane (MSM) modulate fundamental aspects of osteoarthritis pathology, while others such as krill oil and Boswellia serrata target novel inflammatory pathways that can contribute to pain, swelling and joint degradation (Min 2006; Wang 2004; Palmieri 2010; Gregory 2008; Deutsch 2007; Sengupta 2010; Sengupta 2011).

Upon reading this protocol, you will learn about the critical medical factors of osteoarthritis, as well as learn about some under appreciated, yet potentially dangerous side effects of drugs often used to treat osteoarthritis pain. Additionally, you will discover several natural treatment strategies that have been shown to help support joint structure and function to provide more than just pain relief.

Arthritis – Osteoarthritis

Understanding Osteoarthritis

Normal Joint Anatomy and Function

The bones of the human skeletal system are connected by a complex series of joints, which connect two or more bones and allow for a wide variety of movements that would otherwise be impossible (Briant 2008).

In order to facilitate smooth joint movement, the surfaces of joints are lined by a low-friction, load-distributing, wear-resistant tissue called articular cartilage, which is composed of 65 to 80 percent water, collagen (fibrous proteins), proteoglycans, and chondrocytes (cells that produce cartilage) (Pearle 2005). In adults, damaged cartilage has a very limited capacity for self-healing due to blood supply limitations, and the relatively poor capacity of resident chondrocytes to migrate and proliferate (Henrotin 2009).

Joints can be classified as synovial, fibrous, or combination joints, based on the presence or absence of a synovial membrane and the amount of motion that occurs in the joint.

Normal synovial joints allow a significant amount of motion the articular surface. These joints are composed of the following:

  • Articular cartilage
  • Subchondral bone
  • Synovial membrane
  • Synovial fluid
  • Joint capsule

Normal articular surface of synovial joints consists of articular cartilage surrounded by proteoglycans and collagen. The cartilage protects the underlying subchondral bone by distributing large loads, maintaining low contact stresses, and reducing friction.

Synovial fluid supplies nutrients to the articular cartilage; it also absorbs shock from slow movements, as well as the elasticity required to absorb shock from rapid movements.

Osteoarthritis Onset and Progression

Osteoarthritis (OA) can occur in any freely moving joint in the body, but it most commonly affects load- and stress-bearing joints like the knees, lumbar spine, and hips (Lawrence 2008).

At the onset of OA, where cartilage cells depart from their normal pattern of growth and differentiation, the outermost layer of articular cartilage begins to soften as its protein structure degrades. As OA progresses, this loss of protein content becomes more rapid, affecting deeper and deeper layers of cartilage (Pearle 2005). Eventually, the entire protective layer of cartilage is destroyed as the chondrocytes become completely overwhelmed and unable to reverse the tissue damage.

Because cartilage does not contain free nerve endings, joint destruction is typically not associated with pain until it is considerably advanced. This is a major reason why OA tends to be diagnosed so late in the disease process (Bijlsma 2011; Felson 2005).

With a majority of the protective cartilage now gone, the raw surfaces of the bones become exposed to gradual bone-on-bone erosion. This process inevitably leads to the destruction/deformation of nearly all the joint structures involved in movement, and is often accompanied by chronic inflammation in and around the joint space (i.e., synovial membrane) (Pearle 2005).

In many cases, the bone destruction caused by OA is followed by “remodeling”, which is characterized by bone spurs that grow along the joint margins. Although these bony outgrowths are believed to stabilize the injured joint by increasing bone surface area, they are also a significant source of pain, as joint movement causes them to rub against adjacent bones, nerves, and/or soft tissue (Mayo Clinic 2009; Pearle 2005). The intensity of symptoms can vary significantly, ranging from mild to severe (Strand 2011).

The pain caused by OA is typically worsened upon physical activity. As the disease progresses, however, patients may begin to report pain even when resting. Complaints of stiffness tend to occur more frequently in the morning, and often resolve shortly after awakening. However, any period of prolonged inactivity can cause this stiffness, which is sometimes referred to as “inactivity gelling” (Kalunian 2012b).

In cases of advanced OA, patients often report both physical and psychosocial disability. In fact, along with cardiovascular disease, OA causes more disability than any medical condition among the elderly (Hunter 2009).

Arthritis – Osteoarthritis

The Cause & Risk Factors

Osteoarthritis (OA) arises as a result of a complex interplay of factors such as aging, mechanical forces, joint integrity, local inflammation, genetics, and congenital abnormalities (Kalunian 2012a; Bijlsma 2011).

Risk factors for osteoarthritis include (Seed 2011; Busija 2010):

  • Advanced age
  • Female gender
  • Obesity (see below)
  • History of physical labor
  • High-impact sports
  • Joint trauma
  • Family history

Obesity and Osteoarthritis

Because obesity increases the load and stress on many joints, it appears to be one of the most influential risk factors contributing to the development or advancement of osteoarthritis (OA) (Busija 2010). However, studies of obese patients have identified a high prevalence of OA in non-weight bearing areas (e.g., finger joints) as well (Rai 2011).

Data reveal that fat tissue is a major source of catabolic and pro-inflammatory mediators (i.e., cytokines, chemokines, and adipokines), which are implicated in the process of OA (Rai 2011). In addition, obese patients tend to experience insulin resistance and increased glucose load, which may also contribute to the chronic inflammation and cartilage degradation of OA (Sowers 2010).

Since OA has been linked not only to obesity, but also to other cardiovascular risk factors (e.g., diabetes, dyslipidemia, hypertension, and insulin resistance), researchers have proposed that it might be related to a much larger group of risk factors, called “metabolic syndrome” (Velasquez 2010; Katz 2010).

Recent studies have shown that physical activity and diet programs (alone or in combination) are associated with a reduction in pain, as well as functional improvement among overweight or obese adults with OA (Brosseau 2011). In cases where patients are too obese to engage in physical activity, bariatric surgery has also been correlated with improvements in pain and function among patients with OA of the hip and knee (Gill 2011).

Metabolic Factors Associated with Osteoarthritis

Several interrelated metabolic factors also contribute to osteoarthritis onset and progression; chief among which areinflammation, mitochondrial dysfunction, and oxidative stress.

  • Inflammation– Osteoarthritis (OA), like many other age-related diseases, is tied to excessive inflammation (Goldring 2011).

Over-indulgence in foods rich in pro-inflammatory omega-6 fatty acids and insufficient intake of foods rich in anti-inflammatory omega-3 fatty acids characterizes the dietary pattern of most modern, industrialized nations.

Arachidonic acid (an omega-6 fatty acid) is the raw material used by the body to synthesize numerous inflammatory mediators, including leukotriene B4prostaglandin E2, and thromboxane A2, all of which contribute to pain, swelling, and joint destruction (see figure 1) (Liagre 2002; Devillier 2001; Kawakami 2001).

  • Mitochondrial dysfunction – Mitochondriaare the power cores of our cells; they generate the energy that cells need to function. With age, mitochondrial function deteriorates, leading to a variety of negative consequences (Vaamonde-Garcia 2012; Cillero-Pastor 2008; Blanco 2004).

In the case of OA, dysfunctional mitochondria conspire with inflammation to augment joint destruction. One study found that the inflammatory propensity of chondrocytes was amplified when their mitochondria were dysfunctional. Specifically, mitochondrial dysfunction in chondrocytes is associated with increased reactive oxygen species production and activation of the “master-regulator” of inflammation, nuclear factor-kappa B (Nf-kB) (Vaamonde-Garcia 2012).

Fortunately, adhering to a plant-based diet rich in dietary antioxidants, reduced in saturated fat, and balanced in omega-6 and omega-3 fats, such as the Mediterranean diet (see Nutritional Interventions section below) may be an effective means of targeting several of the metabolic imbalances that affect OA.

  • Oxidative stress – Oxidative stress, which is caused by free radicals, is known to be a factor in cartilage destruction and inflammation. These reactive molecules are also involved in pain perception (Ziskoven 2010).

Hormones and Osteoarthritis

After the age of 50, more women are affected by osteoarthritis (OA) than men (Bijlsma 2011); this female preponderance suggests that hormone abnormalities may influence the progression and development of the disease (Tanamas 2011).

The link between hormones and OA is further supported by evidence linking hormone (e.g., estrogen) deficiencies to an increased risk of osteoarthritis (Parazzini 2003).

In addition, some evidence suggests that hormone replacement therapy can relieve symptoms of OA, especially among postmenopausal women (Song 2004). As a result, Life Extension encourages OA patients to test for hormone deficiencies and correct them when identified.

Further reading is available in the Female Hormone Restoration protocol.

(Aldamiz-Echevarria 2007; Wixted 2010; Simopoulos 2011; Schror 2011; Bengmark 2006; Murias 2004; Oz 2008; Keicher 1995; Prasad 2004; Safayhi 1992)

Arthritis – Osteoarthritis

Symptoms And Diagnosis

Osteoarthritis (OA) is diagnosed based upon medical history and clinical examination (Busija 2010).

Radiographic imaging can aid in the diagnosis of OA. It involves the identification of a variety of anatomic abnormalities such as joint space narrowing, bone spurs, and joint bone deformity (Murphy 2012). However, since many patients with joint abnormalities do not develop symptoms, a diagnosis of OA cannot be made solely upon the basis of positive radiographic images. Likewise, patients with symptoms of OA may not display radiographic evidence (Bijlsma 2011).

A newer method of imaging called delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) provides information about cartilage quality and may offer an improved means of diagnosing OA in the early stages (Siversson 2012). This method involves the intravenous injection of a negatively charged contrast agent, which then diffuses into articular cartilage over at least two hours. An increased concentration of contrast agent (in positively charged areas on the MRI scan) would be indicative of articular cartilage damage in that specific region (Taylor 2009).

Arthritis – Osteoarthritis

Conventional Treatment

Since there is no cure for ostheoarthritis (OA), most available treatments are aimed at controlling pain and maintaining joint function (Kapoor 2011). If OA pain is unable to be controlled with less invasive measures like physical therapy and exercise, treatment options ranging anywhere from intermittent use of analgesics to total joint replacement surgery are available (Strand 2011).

Physical Therapy/ Exercise

In most cases, osteoarthritis (OA) treatment should begin with the safest and least invasive therapies (e.g., exercise) (Sinusas 2012). This is because physical activity is associated with significant health benefits among OA patients (e.g., preventing obesity, conserving physical function, and contributing to normal joint health) (Egan 2010).

Exercise programs consisting of muscle strengthening and range-of-motion movements are associated with significant improvements in OA symptoms (Sinusas 2012). Similarly, aerobic activity can reduce pain and disability in people with OA of the knee (Jansen 2011).

In patients who are either unable or unwilling to participate in vigorous exercise, walking for approximately 30 minutes per day, at least 3 days per week, can contribute to a reduction on OA symptoms (Ng 2010).

Pharmacological Treatment and Other Therapies

Acetaminophen. Acetaminophen is usually the first-line pharmacologic therapy in conventional medicine for osteoarthritis (OA) (Lim 2011; Woodcock 2009). If acetaminophen is unsuccessful, the next pharmacological treatment level varies depending upon patient-specific factors (e.g., treatment success), but usually involves the use of one or more of the following options (Lim 2011; Scheiman 2010; Howes 2011):

  • Topical non-steroidal anti-inflammatory drugs (NSAIDs)
  • Topical capsaicin
  • Oral NSAIDs
  • Intra-articular corticosteroid and hyaluronic acid injections
  • Opioids

The Potentially Lethal Side Effects of Over-the-Counter Pain Medications

In an effort to relieve suffering, many ostheoarthritis (OA) patients turn to non-prescription over-the-counter (OTC) analgesics such as acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs) (Hersh 2007). However, since these drugs do not require a prescription, patients may incorrectly assume that they do not need to be as careful about safety as they would with a prescription analgesic. Therefore, it is important for patients to become educated about serious adverse side effects that can occur with popular non-prescription OTC analgesics (Wilcox 2005).

Acetaminophen is one of the most widely used analgesics in the United States. In 2008, approximately 25 billion doses of acetaminophen were sold in the US alone (FDA 2009). Unintentional acetaminophen overdose is responsible for approximately 15,000 hospitalizations each year, and is the leading cause of acute liver failure in the US (Woodcock 2009).

Patents taking acetaminophen should follow these recommendations (Saccomano 2008):

  • Do not to exceed a maximum dose of 4 grams/day
  • Remember that many prescription pain medications also contain acetaminophen
  • Recognize that acetaminophen is also called APAP, paracetamol, and acetyl-para-aminophenol
  • Do not use with other NSAIDs (without medical consultation), which increase the risk of kidney toxicity
  • Do not take with alcohol, which significantly increases the risk of liver toxicity
  • For those taking acetaminophen for pain relief, aggressive supplementation with hepato-protective nutrients such as N-acetyl-cysteine(NAC) and milk thistle extract may provide a means of reducing drug-induced liver damage (Abenavoli 2010; Bajt 2004).

NSAIDs such as ibuprofen and naproxen are also associated with significant adverse effects such as gastrointestinal bleeding, peptic ulcer disease, high blood pressure, edema (i.e., swelling), kidney disease, and heart attack (Peterson 2010). For example, long-term use of NSAIDs can lead to impaired glomerular filtration, renal tubular necrosis, and eventual chronic renal failure by disrupting prostaglandin synthesis, which can impair renal perfusion (Weir 2002). Even in NSAID users without overt kidney dysfunction, subclinical irregularities in kidney function are often observed (Ejaz 2004).

Aspirin (a type of NSAID) is commonly used to treat minor aches and pains, as well as being recommended at low doses for heart protection and stroke prevention. Aspirin irreversibly inhibits an enzyme called cyclooxygenase-1 (COX-1) in platelets, which is why it poses a greater risk of bleeding (i.e., hemorrhage) than other NSAIDs (Hersh 2007). Therefore, patients taking aspirin should avoid the simultaneous use of anticoagulant drugs and/or alcohol (without talking to their doctor first). Aspirin can also cause mild side effects such as heartburn, nausea, vomiting, stomach ache, ringing in the ears, hearing loss, and rash (NIH 2011).

Arthritis – Osteoarthritis

Emerging Therapies


Tanezumab is an antibody that targets nerve growth factor (NGF), which plays a significant role in pain transmission (Cattaneo 2010). Among patients with osteoarthritis (OA) of the knee, tanezumab was associated with a significant reduction in pain intensity (Felson 2011). However, in June 2010, the FDA put all trials of tanezumab on hold because a significant number of patients taking this drug experienced an unusually rapid progression of joint bone necrosis (Lane 2010). Some researchers claim this bone necrosis occurred because of overuse of the joint (due to the potent analgesic effect of tanezumab). However, the FDA is waiting for more information on the exact cause of this adverse effect before allowing trials to continue (Wood 2010; Lane2010).

Stem Cells

Autologous stem cell transplantation, which utilizes stem cells extracted from one’s own body, as opposed to an embryo, mightreverse painful joint deterioration caused by osteoarthritis (OA)It involves using undifferentiated cells that can develop into almost any tissue—new cartilage, tendons, ligaments, even bone—to replace damaged, arthritic joints (Centeno 2008).

Unlike embryonic stem cells, mesenchymal stem cells (MSCs) have already differentiated to some extent, “committing” to develop into tissues such as bone, muscle, tendon, ligament, and cartilage. They can be found in abundance in bone marrow. Under the proper conditions, MSCs can be induced to differentiate into each of their potential specific tissue types, making them ideal for implanting into damaged joints and bones (Jorgensen 2004).

By using MSCs from your own body (autologous), there is no risk of transplant rejection. There is even evidence that transplanted MSCs exert anti-inflammatory, immune-modulating influences within the joint (Ringe 2009; Chen 2008). This means they can theoretically outperform more traditional transplants, which run the risk of destruction by inflammation.

Two seminal reports presented the results of an early human case-report – an individual with a long history of chronic knee pain that proved unresponsive to surgery (Centeno 2008a; Centeno 2008b).

The patient underwent successful harvest, expansion (through platelet-derived tissue factors), and transplant of his own MSCs into his damaged knee joint. The results were compelling—just one month after the injection the patient’s cartilage surface had expanded by approximately 20%, a gain that was maintained at three months. The meniscus (cartilaginous tissue that provides structural support) was nearly 29% larger in volume at 3 months, indicating vigorous growth and remodeling of previously damaged tissue. The patient’s pain level decreased as well.


Apitherapy, the use of bee venom for medicinal purposes, including relieving joint pain, can be dated back to at least the 5th century BC (Alqutub 2011). More recently, there have been numerous anecdotal reports of bee stings dramatically improving symptoms of OA (Mayo Clinic 2009b). Bee venom, when combined with acupuncture for the treatment of OA of the knee, was associated with a substantial analgesic effect compared to traditional (needle-only) acupuncture (Kwon 2001). Researchers believe that the anti-inflammatory characteristics of bee venom can be attributed to mellitinin, a component of bee venom that is one hundred times stronger than the inflammation-reducing hormone cortisone (Alqutub 2011).

Arthritis – Osteoarthritis

Integrative Interventions

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, which is a structural component similar to glucosamine, is believed to help in the management of OA due to its ability to maintain viscosity in joints, stimulate cartilage repair, and attenuate cartilage destruction (Wang 2004). Chondroitin has been shown to improve hand pain and stiffness in OA patients (Wiley-Blackwell 2011). In addition, clinical trials have shown that chondroitin may have structure-modifying effects on OA of the fingers, as well as the knee (Uebelhart 2008; Wildi 2011). Much like glucosamine, chondroitin has a delayed mode of action, thus requiring 2-3 weeks for therapeutic response (Uebelhart 2008).

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).

Anti-inflammatory Nutrients

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). A novel Boswellia serrata extract called Aflapin® 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).

Additional Support

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.

Arthritis – Osteoarthritis

Life Extension Suggestions

Joint Structure Support

  • Glucosamine sulfate: 400 – 3200 mg daily
  • Hyaluronic acid(as Hyal-Joint™): 40 mg daily
  • Methylsulfonylmethane(MSM): 3000 – 6000 mg daily
  • Solubilized Keratin: 300 mg daily
  • Chondroitin sulfate: 450 – 3600 mg daily
  • S-adenosylmethionine(SAMe): 200 – 1200 mg daily in divided doses


Nutrients To Ease Inflammation

  • Fish oil(with olive polyphenols): providing 1400 mg EPA and 1000 mg DHA daily
  • Curcumin(as highly absorbed BCM-95®): 400 – 800 mg daily
  • Boswellia serrata(as highly absorbable AprèsFlex™): 100 mg daily
  • Korean angelica extract(as Decursinol-50™): 200 mg daily
  • Krill oil(blended with astaxanthin and sodium hyaluronate): 350 mg daily
  • Ginger, standardized extract: 150 – 300 mg daily
  • Undenatured type-II collagen(UC-II®): 10 mg daily
  • Bromelain(enteric coated): 500 – 1000 mg daily
  • Soy and Avocado unsaponifiables: Per label instructions
  • Vitamin D: 5000 – 8000 IU daily; depending upon blood levels of 25-OH-vitamin D



  • Green tea, standardized extract: 725 – 1450 mg daily Vitamin C: 1000 – 2000 mg daily
  • N-acetyl-cysteine(NAC): 600 – 1800 mg daily
  • Milk thistle, standardized extract: 750 mg daily


Additional Support

  • Multivitamin and mineral: Per label instruction
  • Capsaicin(topical): Per label instructions
  • Boron(as calcium fructoborate as patented FruiteX B® OsteoBoron®): 1.5 mg daily
  • Gamma Linolenic Acid(GLA): 300 – 600 mg daily
  • Pyrroloquinoline quinone(PQQ): 10 – 20 mg daily
  • Coenzyme Q10(as ubiquinol): 100 – 300 mg daily
  • Trans-resveratrol: 100 – 500 mg daily