OSTEOARTHRITIS

Plant Power:  Do polyphenols in plants hold the answer to osteoarthritis and pain free joints?

The majority of people suffering from osteoarthritis (OA) understand that there is ‘no cure’ (1, 2) and a lifetime of drugs and eventual joint replacement surgery is inevitable (3).  However, this may not be the concluding story.  Recent studies are shedding nutritional light at the end of a dark osteoarthritic tunnel.  Diet and supplements have been seen to manage painful OA and it’s onset but with varying success.  Glucosamine sulfate as a modifying agent (4) and chondroitin are the most widely used supplements (5) but their efficacy has been disputed (6, 7).  Anti-inflammatory Essential Fatty Acids (EFA’s) in oily fish are proving beneficial (8) especially more recently those found in green lipped mussels (9), and now phytonutrients and polyphenols in plants are joining the OA anti-inflammatory party (1).  But can a plant really pack a punch in the treatment of osteoarthritis?  Can they regenerate where other therapies have failed, or is it still just about prevention and pain relief?

 What is Osteoarthritis?

OA is a ‘multifactorial’ degenerative joint disease mainly in the weight bearing mechanical joints like knees, hips, hands, lumber and cervical spine.  It is the most common muscular skeletal disorder and degenerative joint disease in the elderly (10).  With 8.5 million suffering in the UK (3), the incidence of OA is rising due to an ageing and increasingly obese population (11), which is the strongest modifiable risk factor (12) and is fast becoming an economic burden (1). 

OA Degeneration Explained

 Osteoarthritic progression is cyclical and therefore slow, occurring over many years or decades.  Initially, joint cartilage and surrounding tissues interact in response to the normal ageing process of ‘wear and tear’ (primary) or a pre-disposing factor like injury or deformities (secondary) (17).  Joints initially appear normal but are painful and stiff especially in the mornings (18).  Enzymes that increase rates of reactions, like Matrix Metalloproteinase (MMP’s) degrade the joints extracellular matrix that provides structural and biochemical support to the surrounding cells, resulting in the break down of collagen fibrils (19).  This decomposition triggers an increase in hydration changing the joint surface, affecting the joint capsule, subchondral bone, ligaments, muscles and tendons, including the lubricating synovial fluid, which provides oxygen and nutrients to the cartilage.  Muscle weakening increases instability, which degenerates joints further with loss of the articular surface creating bone spurs causing inflammation and more pain, swelling, and loss of function (20, 21).  Sufficient cartilage self-regeneration is not possible and without intervention, degeneration progresses (22).

Normal Joint                                    Osteoarthritis 

(23)

Inflammation is a vital physiological function essential to heal and protect, but with intensity and longevity it becomes pathophysiological or harmful (18).  Inflammatory mediators like cytokines (Interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandins and leukotrienes) are raised in OA so play a role in degeneration (24).  Evidence suggests that osteoarthritic progress is driven by Oxidative Stress (OS), an early sign of ageing (25).  Cartilage damage increases Nitric Oxide (NO) and redox derivatives like reactive oxygen species (ROS) that damage cell structures.  Nitric Oxide is stimulated by inflammatory cytokines further inducing apoptosis or the death of healthy chondrocytic cells (20).  Worse, without sufficient dietary antioxidants like Vitamin (Vit) C, E, superoxide dismutase (SOD’s) or glutathione they cannot be neutralised and cleared from the body (26) increasing damage.  Bacteria and their fermentation process also defends against toxic ROS (27).

OA Degenerative Cycle

 OA Risk Factors

Those predisposed and more likely to suffer from OA are; over forty fives possibly due to joint misalignment, susceptibility to trauma and OS; and those with a genetic predisposition (15) like Europeans (112), women (13), congenital deformities, joint misalignment or High Bone Mineral Density phenotypes (16).

OA is more probable in obese individuals due to the extra stress on joints and release of inflammatory mediators from fat cells increasing inflammation (107).  Other triggers of OA and inflammation include trauma (14) or mechanical stress (3) to joints due to repetitive manual occupations, or a sedentary lifestyle, and inflammatory diseases and infection.  Oestrogen protects cartilage from inflammation so its depletion during the menopause directly affect articular cartilage and can increase triggers of OA (108).

OA Risk Factor Overview (3, 14)

OA Diagnosis & Tests

Osteoarthritis is diagnosed if a person is over 45 years and has activity related joint pain and some stiffness (14).  Other physical and observational tests also diagnose osteoarthritis and blood tests, radiographs and MRI scans can establish type and extent of degeneration but do not reflect the associated pain (3)

OA Conventional Treatment

 There has been a shift in medical treatment of OA to more active, patient-focused management with advice (109).  It aims to include education, weight-loss advice, physiotherapy with moderate exercise, topical pain relief and gait correction (orthotics, crutches or cane) (3).

However, conventional treatment to control inflammatory pain and stiffness with drug therapy, like analgesics, is also advised.  Acetaminophen (Paracetamol) works centrally on the brain temporarily reducing pain, but recent studies have identified them as having reduced effect on OA and are no longer prescribed automatically (14).  Non-steroidal anti-inflammatory drugs (NSAID’s) specifically inhibit inflammatory pathways like cyclooxygenase (COX) and lipoxygenase (LOX) which reduces peripheral and central prostaglandins and the inflammatory response (30).  In severe osteoarthritis or those with Cardiovascular (CVD) issues, opiods can relieve pain (31), these influence cerebral opiate receptor systems inducing a morphine-like effect.  Tramadol for example is a serotonin norepinephrine reuptake inhibitor (32).  Lastly, corticortisoid (33) or more controversially Hyaluronic acid (34, 35) can be injected directly into the joint and have anti-inflammatory effect on the synovium and chondrocytes (105) giving relief.

 These drugs however, have adverse effects depending on the type, dose, length of use and age of client (36).

Joint replacement surgery is recommended for advanced osteoarthritis with persistent pain that affects daily life, despite drugs and alternative therapy (47, 3).  Over 200,000 joint replacements are performed each year in England and Wales (48).

Due to the side effects of drugs and prospect of joint replacement surgery, it is unsurprising that 47% of OA sufferers seek further alternatives to conventional treatment including massage, saunas (24 p415, p561) or acupuncture (20; 49) as well as nutritional and supplement advice (2).

Nutritional Developments

Balancing Essential Fatty Acids (EFA’s)

It is becoming acknowledged that increasing Omega 3 EFA’s (linseeds and oily fish) balances the more common consumption of Omega 6 (vegetable oils, dairy and meat).  This increase disturbs the pro-inflammatory cascade and modifies OA inflammation, OS and signs of ageing (50 p172; 51).  However, the lesser known Omega 3 eicosatetranoic acid (ETA) found in Green Lipped Mussels (105) has also been seen to re-establish protective fluids within joints (8, 52).  Although its mechanism of action is not clear, research suggests that its molecular structure (20:4) is so similar (53) to pro-inflammatory Arachodonic acid (AA) that it may mimic it, competing for enzymes, taking its place (54) and building anti-inflammatory protective defense fluids within joints (8, 52)

Plant Power

Phytonutrients including polyphenols are naturally occurring organic chemicals in plants (pomegranate, green tea, ginger, tumeric and rosehip) (94, 95) that protect them against their environment (55).  Each plant has it’s own unique composition and therefore individual synergistic protective benefit that scientists are attempting to utilise (103).  Most have antioxidant effects mopping up ROS, and others compete higher up the inflammatory pathway (56).  It is thought that increasing dietary polyphenols increase systemic and tissue concentration of polyphenols that then inhibit the progression of OA (1).  They are anti-inflammatory, anti-catabolic stopping muscle breakdown and protective against OS (57).  They promote the increase of chondrocyte and synthesis of collagen therefore encouraging regeneration (1, 58) and are safe (110).

COX – Cyclooxygenase, CRP - C-reactive protein, GAG - Glycosaminoglycans, IL – Interleukins, MMP - matrix metalloproteinases, NO – Nitric Oxide, TNF-a - Tumor necrosis factor alpha

Polyphenols’ positive modifying effects (2) on OA symptoms, regeneration of cartilage and collagen, and inhibition of degeneration (1) gives confidence in them as a therapeutic alternative.  However, it is unclear what plant and dose is required to make significant improvements, so further research is needed (2).

OA Nutritional Strategy

The earlier OA is diagnosed the better the possible outcome (59).  However, at all stages of OA diagnosis it is important to reduce triggers like excess weight and mechanical stress, and mediate OS, inflammation and degeneration.

WHAT TO DO…

 The Mediterranean (62) and Paleolithic (61) diets have been associated with improving OA (63) and they both include good quality, clean and fresh foods like fruit, vegetables, herbs and oily fish.  However, a varied yet individualised nutritional and lifestyle plan should be advised, addressing specific triggers and risk factors like obesity, ageing, symptoms of inflammation, OS and degeneration (60). 

Diet Comparison

Eat Plants

It is important to eat a varied diet high in colourful fruit, vegetables and herbs like berries (100), pineapple, melon, pomegranate, grapes (99), apples (98), turmeric, ginger and green tea (1).  These contain antioxidants (Vit A, C, E, superoxide dismutase (SOD), Glutathione (104)) (96) and phytonutrients (polyphenols 101)) that reduce cell death and OA degeneration, decreasing OA inflammatory activity, reducing OS and signs of ageing (1, 66).  Extra fibre should also regulate body weight and feed beneficial bacteria reducing inflammation (67).   Red wine may also be beneficial due to its polyphenol content (68; 69).

Eat Healthy Fats

Include linseeds and oily fish, high in Omega 3 that are anti-inflammatory (51).  ETA in green lipped mussels may regenerate cartilage but would need to be taken as a supplement (52).  

Eat Protein

Lean meat, fish , eggs, nuts, seeds and pulses - assist muscle strength (70) and also include l-lycine which modulates joint fluids and affect inflammatory mediators in chondrocytes (71). 

Add nutrients

Include nuts and seeds containing selenium required for cartilage regeneration (72).  Copper (nuts), magnesium (seeds & green vegetables) (73) and manganese (pineapple) assist super antioxidant glutathione to mop up ROS and minimize OS (74).  B Vits (B 6,1,2) can be found in whole-grains, improve joint mobility and muscle function (75).  Beneficial bacteria in live natural yogurt (97) should also improve OA pain, inflammation and regeneration (111).

Avoid processed food

These are high in pro-inflammatory trans fatty acids and saturated fat (81), sugar which accelerates OA onset (82), refined carbohydrates like white bread and pasta, and salt.  This should reduce weight, inflammation and joint degeneration (83). 

Nightshade foods like potatoes, tomatoes and peppers effect 10% of arthritis sufferers so is possibly worth eliminating to assess improvements (75). 

Avoid beer (84) as it could increase risks of OA. 

Lifestyle

Weight-loss is important as research suggests obese individuals have greater than 40% increased risk of replacement surgery (87).  Moderate exercise builds muscle tone (14) and has seen protective and anti-inflammatory benefits (89).  Reducing mechanical stress, and work related repetitive or load bearing joint stressors (85) may also alleviate onset and symptoms.  Physiotherapy, ultrasound, massage and sauna therapy may relieve pain (24 p415, p556, 88). 

Avoid cooking at high temperatures as this produces advanced-glycation end products (AGE) increasing OS and degeneration (83, 86).  Consider increasing time outside for adequate sunlight exposure improving Vit D stores, which should decrease stress fracture and muscle injury (79) and is effective for weight-loss (80) but is possibly ineffective for regeneration (76, 77, 78).  Water consumption is important for general health but it has many functions in OA; it removes toxins and ROS from affected joints, helps weight loss, and improves blood circulation to relieve inflammation (90).

Suitable Tests

To help develop an even more specific dietary and lifestyle plan (93), it would be appropriate to test for; a deficiency in Vit D for general bone health, OS biomarkers like 8 hydroxy 2 decoyduanosin or telomeres (91; 92) to indicate and monitor ageing, inflammatory biomarkers (ERS, C-RP) to monitor OA progression, and an EFA profile could determine Omega 3 deficiencies. 

Nutritional & Lifestyle Summary

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