1. By Dr. Hany Mohamed Aly, M.D. Rheumatology lecturer AL-Azhar University

2. What to eat?What to drink? Glucosamine and Chondroitin

3. Evans, C.H.; et al. 2011 There is currently no cure for OA, and there are no therapies which slow or arrest OA progression. So far, most treatments primarily focus on the secondary effects of the disease, such as relieving pain and improving joint function, but fail to address the evolving and complex nature of OA.

4. Akhtar, N and Haqqi, T.M. 2012 Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. urgent need for OA disease-modifying therapies, which can improve symptoms, and are safe for clinical use over long periods of time.

5. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly prescribed, generally decrease pain and improve function, but have no demonstrated beneficial effect on chondroprotection or OA disease prevention and modification. limited efficacy and are associated with a number of potentially serious toxicities including renal insufficiency and gastrointestinal bleeding.

6. This led to the development of more cyclooxygenase-2 selective agents. However, despite some improvement in gastrointestinal safety, no increased efficacy has been observed, and additional safety concerns have surfaced (ie, cardiovascular events).

7. Nutraceuticals—food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease Offer not only a safe alternative to current pharmacologic therapies, but may exert disease and symptom- modification effects in OA. 47% of adults use non-prescribed alternative medications (including food supplements and nutraceuticals) for OA management. Akhtar, N and Haqqi, T.M. 2012

8. Nutraceuticals have been proposed to supplement the required substrate for the repair of cartilage and connective tissues needed for maintenance of optimal cellular function. Investigators are currently defining the role of neutraceuticals treatment and prevention OA.

9. Glucosamine and chondroitin sulphate are among the most common nutraceuticals used for the treatment of OA. Despite the large number of studies examining the efficacy, studies tend to show that these drugs result in little improvement compared with placebo in both symptomatic and structural outcomes.

10. These clinical trial findings may be due to the complexity and challenge of OA treatment, in addition to the effectiveness of dose, route of administration, and quality of the various products. Understanding the mechanism of action of glucosamine and chondroitin sulfate may provide better guidance for clinical use.

11. Clinical and Clinical Effects of Phytoflavonoids, Polyphenols, and Bioflavonoids Nutraceuticals on OA Green Tea Green tea is one of the most commonly consumed beverages in the world and is a rich source of polyphenols including epigallocatechin 3-gallate (EGCG). EGCG has strong anti-oxidant activity, up to 25−100 times more potent than Vitamin C and E.

12. There is strong evidence in small animal studies for advancing green tea-based therapies toward clinical application. Daily administration of green tea extracts in drinking water slowed progression of arthritis in rat adjuvant-induced arthritis, inhibited serum levels of IL-17, and increased serum levels of IL-10. Marotte, H.; Ruth, J.H. et al; 2010

13. Pomegranate Pomegranate fruit is used in traditional medicines to treat inflammation and pain in diseases including arthritis. Pomegranates are considered to have strong anti- oxidant properties due to their high content of soluble polyphenols hydrolyzable tannin and punicalagin.

14. Pomegranate is also rich in anthocyanins, a polyphenolic compound that exhibits anti-oxidant and anti-inflammatory capabilities. In the mono-iodoacetate OA mouse model, pomegranate juice administered by oral gavage for two weeks significantly reduced cartilage damage and proteoglycan loss, especially in the groups receiving the higher doses. Hadipour-Jahromy, Mand Mozaffari-Kermani, 2010

15. Ginger A randomized, placebo-controlled, crossover study comparing ginger extracts and ibuprofen was performed and the study revealed significant improvement in symptoms for both groups before crossover. After the crossover, no difference was noted between the ginger- and placebo-treated groups. Bliddal, H.; Rosetzsky, A. et al; 2000

16. A randomized, double-blind, placebo-controlled trial also studied the effects of ginger and galangal extracts, a spice that is closely related to ginger, in the treatment of knee OA. OA patients treated with ginger and galangal extracts showed greater improvement in pain compared to the placebo group. Altman, R.D. and Marcussen, K.C. 2001

17. Rosehip Powder Rosehip powder is extracted from fruits of the rose plant, and has been used extensively in traditional medicine. A meta-analysis of randomized controlled trials (RCTs) showed rosehip powder reduced pain and led to reduced use of analgesics in OA patients. Mobasheri, A. 2012

18. Vitamin D OA was traditionally considered as a cartilage disease, characterized by cartilage degeneration. But many evidences, as osteophytosis, subchondral bone sclerosis and cyst formation have grown up and demonstrated the prominent role played by subchondral bone in OA pathophysiology.

19. Low serum levels of vitamin D may increase the progression of knee OA Impair the ability of bone to respond optimally to OA pathophysiologic processes. Predispose patients to joint degradation. High prevalence of low vitamin D status has been demonstrated in persons with knee OA.

20. A high prevalence of 25 (OH) D deficiency (70%) was detected in our cohort of medial femoro-tibial knee OA patients, independently of BMI, age or gender. Significant medial meniscal degeneration was detected after 1 year only in the knees of our female patients who were vitamin D deficient, suggesting that deep vitamin D deficiency might play a role in OA progression. Probing the relation between vitamin D deficiency and progression of media femoro -tibial Osteoarthitis of the knee. Hassan Bassiouni 1, Hany Aly 1, Khaled Zaky 1, Nouran Abaza 2,Thomas Bardin 3.

23. Glucosamine/Chondroitin Arthritis Intervention (GAIT Trial). In 2006, the U.S. National Institutes of Health (NIH) funded a 24 week, 12.5 million-dollar multicenter clinical trial (the GAIT trial).U.S. National Institutes of Healthmulticenter clinical trial chondroitin sulfatechondroitin sulfate, glucosamine hydrochloride, chondroitin/glucosamine in combination, and celecoxib.celecoxib two groups of patients with osteoarthritis of the knee: Patients with mild pain (n=1229), and patients with moderate to severe pain (n=354).

24. No statistically significant difference between groups taking glucosamine HCl, chondroitin sulfate, glucosamine/chondroitin; and those taking an inactive placebo or the positive control, the prescription analgesic celecoxib.statistically significant However, in the moderate-to-severe pain subgroup, the combination of chondroitin and glucosamine was found to be clinically more effective (in 25% of the patients) in treating pain than celecoxib or chondroitin and glucosamine taken individually.celecoxib

25. The study also found chondroitin sulfate to have no significant effect in reducing joint swelling, effusion, or both. These results indicate that glucosamine and chondroitin do not effectively relieve pain in the overall group of osteoarthritis patients, though it may be an effective treatment for those suffering from moderate-to-severe pain.osteoarthritis

26. In a follow-up study, 572 patients from the GAIT Trial continued the supplementation for two years. After two years of supplementation with glucosamine and chondroitin sulfate, alone or in combination, there was no benefit in slowing the loss of cartilage, in terms of joint space width, when compared to a placebo.

28. The Long-term Evaluation of Glucosamine Sulfate (LEGS) study Determine whether glucosamine sulfate, chondroitin sulfate or a combination of both are effective treatments for chronic knee pain due to osteoarthritis.osteoarthritis 502 patients ( 605 enrolled) were followed for two years. The main outcomes were disease progression, as measured by joint space narrowing (JSN) and knee pain (VAS).VAS

29. There was no significant symptomatic benefit detected for these dietary supplements, and a longer study would be required to test the efficacy of both supplements combined. Ann Rheum Dis 2015;74:851-858 doi:10.1136/annrheumdis-2013-203954.

30. Recommendations for Glucosamine and chondroitin. EULAR NICE ORSI 2003 both are recommended for structural and symptomatic effects 2014 glucosamine Not recommended 2014 chondroitin not recommended 2014 glucosamine Not recommended 2014 chondroitin not recommended 2014 glucosamine symptom releif, uncertain 2014 glucosamine disease progression, not recomened 2014 chondroitin symptom releif, uncertain 2014 chondroitin disease progression, not recomened 2014 glucosamine symptom releif, uncertain 2014 glucosamine disease progression, not recomened 2014 chondroitin symptom releif, uncertain 2014 chondroitin disease progression, not recomened 2012 both are conditionaly not recommended ACR

31. Although the current therapeutic approach to OA focuses on symptomatic relief, the ability to modify the incidence or progression of the disease remains a goal of the prescribing physician. Clinical data suggest a potential role for glucosamine/CS, however, the ability of these nutraceuticals to change disease outcome remains in need of clearer elucidation. Although safety profiles are reassuring, until there is better efficacy data, the cost of nutraceuticals remains possibly the most significant limiting factor for their initiation.

32. Thank you