Dietary Supplementation With Blueberry in OA

Highbush Blueberry Supplementation for Osteoarthritis Pain, Intra-articular Inflammation and Post-operative Recovery in Total Knee Replacement Patients

Osteoarthritis is a painful long term joint condition that is associated with poor quality of life. There are no treatments to prevent it. Inflammation is one cause of osteoarthritis. This inflammation is complex. It involves many joint tissues, like cartilage and fat. It also involves many proteins that act as inflammatory 'signals'. Safely targeting these proteins with medications has so far proved ineffective. Physiotherapy and weight loss can help osteoarthritis, but there is a need for other approaches. Blueberries are rich in natural chemicals called polyphenols; these have well-established anti-inflammatory effects. Blueberries and other fruits may improve osteoarthritis symptoms, but the investigators do not know how this improvement happens. It may be that these foods reduce inflammation within the joint tissues. They will investigate this. This will help us to understand 1) how blueberries improve osteoarthritis symptoms and 2) whether dietary supplementation with blueberries could slow down joint damage in osteoarthritis, rather than just improving symptoms. Additionally, high levels of joint inflammation predict poorer recovery from joint replacement surgery. Therefore, blueberry supplementation may hasten this recovery. Fifty eight people scheduled to have a knee replacement for osteoarthritis will receive either six weeks blueberry supplementation or a placebo pre-surgery. Participants will continue the supplementation for six weeks after surgery. First, this study will use tissue samples (cartilage, fat and the joint lining called synovium) obtained during surgery to investigate the effects of pre-operative blueberry supplementation on markers of joint inflammation. Second, this study will assess the ability of dietary supplementation with blueberries to improve the symptoms of osteoarthritis. Finally, this study will investigate the effect of blueberry supplementation on recovery from total knee replacement. Our investigations may provide evidence to support dietary supplementation with blueberries to slow down osteoarthritis progression and to improve recovery from osteoarthritis joint replacement surgery.

The intervention in this study is 12 weeks of daily blueberry supplementation which is comprised of freeze-dried powdered whole blueberries i.e., blueberries with water removed.

The intervention in this study is 12 weeks of daily maltodextrin supplement used to mimic the carbohydrate composition of whole blueberries.

Concentration of TNF-ALPHA gene expression in joint tissue (synovium, infrapatellar adipose tissue and cartilage)

Using multiplex immunoassay including but not limited to at TNFα, IL-6, IL-10 and IL-1β, MIP1α, Galectin 1, Chemerin, Eotaxin, gp130, MCP-1, IL-7, MIP3α, IL-15, Aggrecan, Resistin, Leptin, MIP1β, MMP-1, MMP-3 and MMP-13

Concentration of broad panel of Inflammatory and pro-cartilage degradative gene and protein expression markers

Using RTqPCR and immunoblotting including but not limited to TNFα, IL-6, IL1β, IL-8, IL-10, IL-18, IL-7, IL-15, MCP1, LEP, ADIPOQ, NAMPT, RETN, TGFB1, MMP1, MMP2, MMP3, MMP9, MMP13, TIMP1, TIMP2, TIMP3, TIMP4, ADAMTS4, ADAMTS5, , ACAN, COL1A1, COL2A1, COL13A1, COL14A1, COL15A1, DKK1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL20, CX3CL1, CCR3, CCR2, LGALS1, RARRES2, and IL6ST

Inclusion Criteria: Participants capable of giving informed consent Sex: Male and female Age: > 40 years - Those under 40 are more likely to have an undiagnosed secondary cause of osteoarthritis BMI: > 18 kg/m2 Listed to have a total knee replacement for osteoarthritis Participants are permitted to participate in other ongoing surgical intervention studies, as long as these are not trials of a dietary supplement or a medication. Exclusion Criteria: Those who have received intravenous or oral immunosuppressant medications in past 2 years Those who have had intra-articular steroid injection in 6 months preceding surgery. Some secondary causes of osteoarthritis (mechanistic confounders that are likely to influence tissue inflammation measures: Known congenital joint disorders Other inflammatory arthritis e.g. rheumatoid arthritis Avascular necrosis, infectious arthritis Paget disease Osteopetrosis Osteochondritis dissecans Hemochromatosis Wilson's disease Hemoglobinopathy Ehlers-Danlos syndrome Marfan syndrome Acromegaly Those typically consuming more than eight 80 g portions (or juice equivalent) of blueberries, blackberries, strawberries, raspberries, blackcurrants, pomegranate or cherries per week Those with a known fruit allergy, for which they carry an adrenaline auto-injector or have required anti-histamine, adrenaline, glucocorticoid or beta-agonist treatment. Those who cannot adequately understand verbal explanations or written information given in English