Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients’ overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient’s risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis.
Best practice guidelines for chronic osteoarthritis focus on self-management, that is, weight control and physical activity, and on pharmacological support for inflammation and pain [
To establish the prescription of optimal nutrition and physical activity as ‘‘first-line’’ interventions for low-grade inflammation associated with chronic osteoarthritis, we have synthesized three primary lines of support: (1) the literature that supports that the western diet and inactive lifestyle are proinflammatory, and a plant-based diet and regular physical activity are anti-inflammatory; (2) the literature supporting that low-grade inflammation is common across lifestyle-related conditions including osteoarthritis; and (3) evidence-informed recommendations for effecting lifestyle behavior change that can be readily integrated by health practitioners into ‘‘first-line’’ management. We conclude with implications for clinical practice and research with respect to its paradigm and avenues for future investigation.
Human lifestyles have changed dramatically over millennia. With technological and economic advancements in western countries particularly over the past 60 years, lifestyle-related conditions are the leading causes of premature death [
The factors associated with the typical western lifestyle that impact people’s health have been elucidated by cross-cultural studies including seminal work related to Mediterranean diet and exercise patterns and Asian lifestyles. The Mediterranean diet known to be health protective is largely plant based, favors olive oil over animal fats, and is high in fiber, vegetables, and fruits [
In addition, sedentary living and inactivity are hallmarks of western culture. Evidence supports that inactivity is proinflammatory and augments oxidative stress [
Other lifestyle traits common in western culture are also known to be proinflammatory. Smoking, for example, remains prevalent despite some success in recent decades in reducing its prevalence through public health campaigns. The chronic low-grade inflammation associated with smoking [
Thus, prescribing healthy living strategies in general as well as optimal nutrition (of which weight loss is an additional benefit) and regular physical activity are warranted as being first-line interventions in clinical practice guidelines for conditions such as osteoarthritis associated with chronic low-grade inflammation. These conditions are described in the next section and often coexist as comorbidities in people with osteoarthritis.
Figure
Relationships among osteoarthritis, obesity, and physical inactivity and relationship to the etiology of chronic low-grade systemic inflammation. Adapted from [
Table
Synthesis of evidence of chronic low-grade inflammation being associated with osteoarthritis.
Authors | Title | Evidence |
Methods | Findings | Conclusion |
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Cecil et al., 2005 |
Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products | Basic science study |
Analysis of human cartilage, cultured human articular chondrocytes, and recombinant human S100A11, soluble RAGE (advanced glycation end products), and RAGE-specific blocking antibodies | Normal human knee cartilages showed constitutive RAGE and S100A11 expression, and RAGE and S100A11 expression were upregulated in OA cartilages | Up-regulated chondrocyte expression in OA cartilage and RAGE signaling promote inflammation-associated chondrocyte hypertrophy |
Rojas-Rodríguezet al., 2007 |
The relation between the metabolic syndrome and energy-utilization deficit in the pathogenesis of obesity-induced osteoarthritis | Narrative review to examine a medical hypothesis: |
Evidence search strategy unspecified | Increased TH1 cytokines are produced by macrophages in presence of chronic infection and suppress insulin sensitivity |
The fatigue and muscle weakness induced by insulin resistance and inflammation in obese patients with metabolic syndrome (pro-inflammatory state) increase trauma to joints that result in breaking of tenoperiosteal junction and abrasive damage of cartilage |
Schlesinger and Thiele, 2010 |
The pathogenesis of bone erosions are in gouty arthritis | Review |
Synthesis of mechanical, pathological, cellular, and immunological factors role in the pathogenesis of bone erosions in gouty arthritis |
Monosodium urate crystal deposition associated with underlying OA |
Tophus eroding underlying bone is pivotal for development of bone erosions in gouty arthritis |
Smith et al. 1997 |
Synovial membrane inflammation and cytokine production in patients with early osteoarthritis | Clinical trial of patients with varying stages of early OA ( |
Synovial membrane samples obtained from the knees of patients | Thickening of lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes; changes proportional to severity |
Chronic inflammatory changes with production of pro-inflammatory cytokines characterize the synovial membranes of patients with early OA |
Synthesis of evidence of chronic low-grade inflammation being associated with conditions that may coexist with a diagnosis of osteoarthritis.
Alzheimer’s disease | |||||
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Giunta et al., 2008 |
Inflammaging as a prodrome to Alzheimer’s disease | Review |
Articles reported the characterization the aging immune response related to the concept of inflammaging (low-grade chronic up-regulation of pro-inflammatory response) |
Conditions of increased innate immune response with overproduction of pro-inflammatory proteins are related to healthy aging and AD |
Countering inflammaging may prevent or treat the symptoms of AD |
Veerhuis, 2011 |
Histological and direct evidence for the role of complement in the neuroinflammation of AD (AD-Alzheimer’s disease) | Histologic and direct evidence | Synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines, and other potentially neurotoxic agents by the glial cells implicated in |
In AD, there are brain areas with amyloid deposits and complement activation products |
Evidence from immunohistochemical, in vitro and animal studies points to role for complement activation |
Candore et al., 2010 |
Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement | Review | Search strategy unspecified | Evidence supports that low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality with ageing | Elucidation of ageing pathophysiology to disentangle age-related low-grade inflammation will provide evidence to develop drugs to delay ageing process |
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Asthma | |||||
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Chou et al., 2011 |
Asthma and risk of erectile dysfunction—a nationwide population-based survey | Population-based survey |
Cohorts were followed for evidence of erectile dysfunction (ED) | Subjects with asthma experienced 1.9-fold increase in ED independent of age and comorbidity compared with control cohort | Asthma may be an independent risk factor for ED (increasing with asthma severity) |
Dixon, 2012 |
The treatment of asthma in obesity | Expert review | Epidemiology of obesity has influenced epidemiology of other conditions, for example, asthma |
Mechanical factors, metabolic inflammation, and other comorbidities probably contribute to asthma | Therapies need to be developed and tailored to various underlying mechanisms |
Juel et al., 2012 |
Asthma and obesity: does weight loss improve asthma control? A systematic review | Systematic review | Obesity associated with high asthma incidence and poor control |
Weight loss in obese individuals associated with 48%–100% remission of asthma symptoms |
Weight loss consistently reduces asthma symptoms |
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Atherosclerosis | |||||
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Gu et al., 2012 |
Psychological stress, immune response, and atherosclerosis | Review | Synthesis of evidences that various immunological factors are transformed under prolonged psychological stress by causing vascular low-grade inflammation | Evidence supports expression of pro- and anti-inflammatory cytokines by stress hormones (catecholamines and corticosteroids) | Elucidation of two-way communication between neuroendocrine and immune systems Implications for targeted treatment strategies |
Kucharz, 2012 |
Chronic inflammation-enhanced atherosclerosis: can we consider it a new clinical syndrome? | Narrative review |
The literature search strategies unspecified | Chronic inflammation-enhanced atherosclerosis syndrome is proposed as a separate syndrome occurring in patients suffering of chronic inflammation | Atherosclerosis as an inflammatory disease and chronic extravascular inflammation have common mechanisms resulting in an increase in atherosclerosis and its sequelae, CVD |
Lu et al., 2012 |
Unpredictable chronic mild stress promotes atherosclerosis in high cholesterol-fed rabbits | Experimental | Chronic psychological stress associated increased with risk of atherosclerosis |
High-cholesterol feeding resulted in hypercholesterolemia and formation of atherosclerotic plaques in the aorta |
Findings support that atherosclerosis is augmented by chronic psychological stress, due to increased vascular inflammation and decreased endothelial nitric oxide bioavailability |
Ortega et al., 2012 |
White blood cell count is associated with carotid and femoral atherosclerosis | Clinical study |
Examined the association between inflammatory markers and atherosclerosis evidence |
Chronic low-grade inflammation is associated with atherosclerosis |
WBCC is a useful and easy marker of atherosclerosis, consistent with its inflammatory basis |
Pinto et al., 2012 |
Effects of physical exercise on inflammatory markers of atherosclerosis | Expert narrative review | Synthesis of research related to regular physical training and low-grade |
Physical exercise could be considered a useful weapon against local vascular and |
Several mechanisms explain the positive effect of chronic exercise |
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Cancer | |||||
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Correa and Piazuelo, 2012 [ |
The gastric precancerous cascade | Lead article |
Review of experimental articles that support the steps in the gastric precancerous cascade |
Inflammatory changes may persist throughout the precancerous process |
Most promising strategy for control of the condition is prevention, augmented by prolonging the pre-cancerous process which requires an understanding of the precancerous cascade |
Peters et al. 2012 |
Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice |
Experimental |
Outcomes based on colonoscopic evaluation and protein analysis | CSC mice showed accelerated macroscopic lesions |
Findings consistent with the fact that chronic psychosocial stress increases the likelihood of developing an irritable bowel, and multiple types of malignant neoplasms, including CRC |
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Chronic obstructive lung disease | |||||
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Cox jr 2012 |
Dose-response thresholds for progressive diseases | Narrative review |
Framework proposed for understanding how exposure can destabilize normally homeostatic |
The resulting model, called the alternative equilibria (AE) theory, implies the existence of an exposure threshold below which transition to the |
These predictions may help to explain patterns observed in experimental and epidemiological |
variables, |
state will not occur, and once exceeded, |
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Lindberg et al., 2011 |
Co-morbidity in mild-to-moderate COPD: comparison to normal and restrictive lung function | Clinical trial |
To evaluate if conditions associated with systemic inflammation (e.g., cardiovascular diseases, diabetes, chronic rhinitis, and gastroesophageal reflux, are overrepresented in patients with COPD |
Prevalence of chronic rhinitis and gastroesophageal reflux (GERD) was higher in COPD compared to reference group |
Co-morbid conditions associated with systemic inflammation, for example, cardiovascular disease, chronic rhinitis, and gastroesophageal reflux, were common in patients with COPD |
ten Hacken, 2009 |
Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease? |
Review |
Physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases |
High prevalence of asthma in obesity |
Elucidation of the independent relationship between physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are needed |
independent of body mass index Obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome | |||||
Wouters et al., 2009 |
Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection? | Review |
To examine the association between asthma and chronic obstructive pulmonary disease (COPD) |
Spillover of inflammatory mediators into the circulation considered the source of systemic inflammation in these conditions |
Nature of systemic inflammation remains unclear |
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Diabetes mellitus (types 1 and 2) | |||||
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Chang et al., 2012 in press |
Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus |
Clinical trial |
To examine whether short- or long-term glycemic fluctuations could induce oxidative stress and chronic inflammation, relationships between glycemic variability, oxidative stress markers, and high-sensitivity C-reactive protein (hs-CRP) were studied |
Relationships between markers for short- and long-term glycemic control remained significant with respect to oxidative stress and chronic inflammation, after adjusting for other markers of diabetic control | Both acute and chronic blood glucose variability can induce oxidative stress and chronic inflammation |
van Bussel et al., 2012 in pressNutrition and Metabolism in Cardiovascular Disease [ |
Unhealthy dietary patterns associated with inflammation and endothelial dysfunction in type 1 diabetes: The EURODIAB study |
Clinical trial |
A healthy diet has been inversely associated with ED and LGI |
Consumption of less fibre, polyunsaturated fat and vegetable protein, and more cholesterol over the study period was associated with more ED and LGI | Following dietary guidelines in type 1 diabetes may reduce cardiovascular disease risk by favourably affecting ED and LGI |
1997 and averaged into |
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Fibromyalgia | |||||
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Kadetoff et al., 2012 |
Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels |
Clinical trial |
To assess intrathecal concentrations of pro-inflammatory substances in patients with FM | Elevated cerebrospinal fluid and serum concentrations of interleukin-8, but not interleukin-1beta, in FM patients | Findings consistent with a central pro-inflammatory component |
Ortega et al. 2012 |
Aquatic exercise improves the monocyte pro- and anti-inflammatory cytokine production balance in patients with fibromyalgia (FM) |
Clinical trial |
Evaluated the effect of a pool-aquatic exercise program (8 months, two weekly 60 min sessions) on the inflammatory cytokine production by isolated monocytes, and on the serum concentration of C-reactive protein (CRP) | Monocytes from FM patients released more inflammatory cytokines than those from women in control group |
FM is associated with chronic inflammation that can be offset with physical exercise such as aquatic exercise |
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Hypertension | |||||
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Berni et al., 2012 |
Renal resistive index and low-grade inflammation in patients with essential hypertension |
Clinical trial |
To study the relationship between RRI and serum hsCRP in hypertensives with preserved renal function, without | Patients with pathologic RRI ( |
HsCRP is a predictor of both pathologic RRI and decreased RV/RRI, even after adjustment |
failure, microalbuminuria, or major inflammatory disease | microalbuminuria | with decreased RV/RRI ( |
low-grade inflammation is associated with tubulointerstitial damage | ||
He et al., 2012 |
Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial | Randomized, double-blind, placebo-controlled trial |
To explore whether metformin-based treatment (which reduces weight and inflammation in diabetes) benefits obesity-related hypertension without diabetes |
Metformin compared with placebo did not have effects on blood pressure, blood glucose, and high-density or low-density lipoprotein cholesterol, but it did reduce total serum cholesterol |
Results supported an inflammatory component of hypertension in patient who are obese, that was amenable to metformin that targets inflammation |
Sari et al. 2011 |
The effect of quinapril treatment on insulin resistance, leptin and high sensitive C-reactive protein in hypertensive patients | Clinical trial |
To evaluate the effect of quinapril on HOMA-IR, high sensitive C-reactive protein, and leptin |
After treatment with quinapril HOMA-IR, high sensitive C-reactive protein, and leptin were decreased in hypertensive patients | Quinapril may be used as a therapy for improving blood pressure as well as the insulin resistant, hyperleptinemic, and low-grade inflammatory state in hypertension |
Sugiura et al. 2011 |
Impact of lipid profile and high blood pressure on endothelial damage | Clinical trial |
Blood was sampled for laboratory analysis and endothelial | Total cholesterol to high-density lipoprotein cholesterol ratio | Impaired endothelial function was associated with increased |
along with gender and age-matched normotensive subjects (both |
function was assessed by flow-mediated dilation (FMD) |
(total-C/HDL-C) was inversely correlated with the FMD value and positively correlated with both malondialdehyde-modified low-density lipoprotein and high-sensitivity C-reactive protein values |
total-C/HDL-C values, possibly as a result of increased vascular oxidative stress and inflammation | ||
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Insulin resistance/metabolic syndrome | |||||
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Piya et al., 2006 in press |
Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin | Review | To examine impact of nutrients such as glucose and lipids on inflammatory pathways, specifically within adipose tissue, and how these influence adipokine inflammation and insulin resistance |
Through overnutrition, glucose, lipids, and endotoxin affect different tissues to mediate an aberrant inflammatory response and augment pathogenesis of insulin resistance and metabolic disease | Evidence supports the persistent insults from dysfunctional diets that need to be the targets of intervention |
Shoelson et al., 2006 |
Inflammation and insulin resistance | Review | Evidence has linked inflammation to the pathogenesis of type 2 diabetes (T2D) |
With discovery of an important role for tissue macrophages, these findings are helping to reshape thinking about how obesity increases the risk for T2D and metabolic syndrome | The evolving concept of insulin resistance and T2D as having immunological components and as improving the picture of how inflammation modulates metabolism provides new opportunities for using anti-inflammatory strategies to address metabolic consequences of excess adiposity |
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Ischemic heart disease | |||||
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Simon, 2012 |
Inflammation and vascular injury | Review |
To examine the |
Binding site for GPIb |
Almost all inflammation is platelet dependent |
Kalogeropoulos et al., 2012 |
From risk factors to structural heart disease: the role of inflammation | Review | Review strategy unspecified | Elevated levels of circulating proinflammatory cytokines and adipokines have been repeatedly associated with increased risk for clinically manifest (Stage C) heart failure in large cohort studies. The role of low-grade, subclinical inflammatory activity in the transition from risk factors (Stage A heart failure) to structural heart disease (Stage B heart failure) is less well understood |
Recent evidence suggests that chronic low-grade inflammatory activity is involved in most mechanisms underlying progression of structural heart disease, including ventricular remodeling after ischemic injury, response to pressure and volume overload, and myocardial fibrosis |
Vizzardi et al. 2011 |
|
Review | Many studies have been performed on the relationship between infection from |
Review of the literature that has investigated the role of HP in the development and pathogenesis of CAD. Infection could lead to IHD through pathways such as endothelial cells | Results from these studies have raised new perspectives on coronary heart disease, especially regarding the possibility of modifying the clinical history of the disease through eradication of these |
Some infections could have a role on the genesis and development of damage to the vascular wall and of atheromatous plaque HP could influence the development of IHD through various pathways |
colonization, changes in the lipid profiles, increased coagulation and platelet aggregation levels, induction of molecular mimicry mechanisms, and the promotion of a low-grade systemic inflammation | infective microorganisms | |||
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Kidney disease | |||||
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Kang et al., 2012 |
Low-grade inflammation, metabolic syndrome and the risk of chronic kidney disease: a 2005 Korean National Health and Nutrition Examination Survey | Cross-sectional study |
To examine the relationship between white blood cell (WBC) count and chronic kidney disease ≥stage 3 |
Low-grade inflammation is associated with chronic kidney disease in people with metabolic syndrome ≥stage 3 | Low-grade inflammation associated with chronic kidney disease ≥stage 3 in people with metabolic syndrome suggests new treatment approaches |
Kocyigit et al., 2012 |
Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients | Clinical trial |
To clarify temporal relationship between ADPKD, hypertension, and the loss of renal function, patients with early-stage ADPKD who did not yet have hypertension were examined |
Despite normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls |
Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR |
Luis- Rodríguez et al., 2012 |
Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy |
Review (experimental and clinical studies) | To identify pathogenic pathways for earlier diagnosis and targeting novel treatments |
Activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy |
Increased knowledge and understanding of inflammatory mechanisms are needed to augment clinical interventions for this complication |
Tang et al., 2012 |
Inflammation and oxidative stress in obesity-related glomerulopathy | Review | To focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity |
Obesity-related glomerulopathy is a major cause of end-stage renal disease. |
Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, and resistin, that affect inflammation |
interventions may be therapies to prevent and |
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Obesity | |||||
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Hulsmans et al., 2012 |
Interleukin-1 receptor-associated kinase-3 is a key inhibitor of inflammation in obesity and metabolic syndrome |
Experimental and clinical studies |
Cluster of molecules were studied that support interactions between the stress conditions of low-grade inflammation and oxidative stress in monocytes |
Visceral obesity is associated with type 2 diabetes and metabolic syndrome |
Weight loss was with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components |
Issa and Griffin, 2012 |
Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation | Review | Search strategy unspecified | Pathobiology of obesity and osteoarthritis (OA) was examined, as well as literature the underlying systemic inflammation, its relationship to inactivity, and their interactions |
Inflammation is central to progression of the disease cycle involving obesity, osteoarthritis, and physical inactivity |
Rico-Rosillo and Vega-Robledo, 2012 |
New trends in macrophages, inflammation and adipose tissue | Review | To highlight the macrophage participation in the generation of obesity-induced inflammation |
Accumulating evidence suggest the involvement of adipose tissue derived proteins, collectively known as adipokines as well as other factors produced in this tissue by cells besides adipocytes, like fibroblasts, lymphocytes, and macrophages |
Obesity is considered a low-inflammatory condition |
Stienstra, 2007 |
PPARs, obesity, and inflammation | Review | To address the role of peroxisome proliferator-activator receptors (PPARs) in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall |
Changes in inflammatory status of adipose tissue and liver with obesity supports co-existent chronic low-level inflammation Various molecular mechanisms have been implicated in obesity-induced inflammation (some modulated by PPARs) |
Obesity is accompanied with fat storage in tissues other than adipose tissue (liver and skeletal muscle) which may lead to local insulin resistance and stimulate inflammation |
Tajik et al. 2012 in press |
Effect of diet-induced weight loss on inflammatory cytokines in obese women | Clinical trial |
To evaluate changes in pro/anti-inflammatory adipocytokines and metabolic profile after moderate diet-induced weight, anthropometric parameters, lipid and glucose profiles, IL-6, IL-10, and IL-18 were measured |
Body mass index, waist circumference, triceps skinfold thickness, total cholesterol, triglyceride, and fasting plasma glucose decreased, while HDL-cholesterol increased |
Obesity is associated with low-grade systemic inflammation which has been linked to the increased risk of cardiovascular disease and type II diabetes in obese patients |
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Rheumatoid arthritis | |||||
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Gremese and Ferraccioli 2011 |
The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk | Review | Rheumatoid arthritis (RA) patients have an incidence of cardiovascular (CV) diseases two-fold that of the general population Atherosclerosis, the main determinant of CV morbidity and mortality, and carotid intima-media thickness, an early preclinical marker of atherosclerosis, also occur early on in RA |
CV risk factors seem to have the same prevalence in RA and non-RA patients, thus they do not fully explain increased CV burden, suggesting that RA inflammation and therapies play a role in increasing CV risk in these patients |
Obesity is now regarded as a systemic, low-grade inflammatory state, and inflammation as a link between obesity, metabolic syndrome, and CV diseases |
on the other hand, there are evidence that adipokines may play a role in inflammatory RA | |||||
Prete et al., 2011 |
Extra-articular manifestations of rheumatoid arthritis: An update | Review |
Current Reviews knowledge about EAM in terms of frequency, clinical aspects, and current therapeutic approaches. In an initial attempt at a classification, we separated EAM from RA co-morbidities and from general, constitutional manifestations of systemic inflammation. EAM was classified as cutaneous and visceral forms, both severe and not severe |
In aggregated data from 12 large RA cohorts, patients with EAM, especially the severe forms, were found to have greater co-morbidity and mortality than patients without EAM | Understanding the complexity of EAM and their management remains a challenge for clinicians, especially since the effectiveness of drug therapy on EAM awaits study |
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Stroke | |||||
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Denes et al. 2011 |
Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target | Review | Inflammation is established as a contributor to cerebrovascular disease |
Evidence supports importance of peripherally-derived immune cells and inflammatory molecules in various central nervous system disorders, including stroke |
Blockade of IL-1 could be therapeutically useful in several diseases which are risk factors for stroke |
to outcome in experimental studies, with growing evidence from clinical research |
inflammation and is a key driver of peripheral and central immune responses to infection or injury | ||||
Wu et al., 2012 |
Risk of stroke among patients with rhinosinusitis: a population-based study in Taiwan | Population-based trial |
Each patient was followed up using data entered until the end of 2006 |
Patients with rhinosinusitis were more likely to suffer strokes than the control population, after adjusting for potential confounders |
Both acute and chronic sinusitis are risk factors or markers for stroke that is independent of traditional stroke risk factors |
Although the degree to which the typical western lifestyle explains the prevalence of osteoarthritis is unclear, maximizing healthy living may have the greatest potential for minimizing its risk, its impact, and long-term outcomes including life-long health and wellbeing compared with invasive interventions including drugs and surgery and their related sequelae and side effects.
Overweight is now considered a leading condition associated with marked inflammation followed by arthritis, heart disease, and type 2 diabetes mellitus [
For lifestyle behavior change to constitute ‘‘first-line’’ management as the literature would support, the health care team overall needs to share this goal and practice in partnership rather than in the conventional siloed care. The three primary health professions excluding, dentistry and pharmacy, include physicians, nurses, and physical therapists. Traditionally, physicians are highly trained in administration of invasive interventions, that is, drugs and surgery. Nurses have assumed a role in patient education over the years along with psychosocial considerations of patient care. Of the established health professions, physical therapy is the leading nonpharmacologic profession that is particularly well positioned to assume such an education role for patients related to healthy lifestyles and exercise [
Consistent with the 21st century epidemiological trends, physical therapists are moving toward a model of care based on health (International Classification of Functioning, Disability and Health) [
Pro- and Anti-inflammatory Foods (Source: reviews Beck, 2010; Daniluk, 2011; Weil, 2012; [
Pro-inflammatory Foods | Anti-inflammatory Foods |
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Alcohol | The “anti-inflammatory” nutritional plan includes: |
Regular high consumption irritates esophagus, larynx and liver which can lead to chronic inflammation which promotes tumor growth at sites of chronic irritation | Avoidance of sweets and sugar |
Avoidance of high refined foods such as processed foods (white bread and rice, and pasta), | |
Cooking oils | Recommended anti-inflammatory foods: |
A diet of high imbalance of omega-6 to omega-3 ratio promotes inflammation (e.g., heart disease and cancer) | Oatmeal (not instant) |
Dairy products |
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Meat (commercially produced meats where animals are fed grains such as soy beans and corns (a diet high in inflammatory omega-6 fatty acids and low in anti-inflammatory omega-3 fatty acids; also, these animals have limited exercise and raised to gain excess fat, ending up with high saturated fats. To make the animals grow faster and prevent them from getting sick, they are injected with hormones and fed antibiotics.) | |
Red meat contains a molecule humans do not naturally produce (Neu5Gc) that leads to the production of antibodies in defense of it, an immune response that may trigger chronic inflammation, and low grade inflammation (linked to heart disease and cancer) |
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Refined grains |
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Devoid of fiber and vitamin B compared with unrefined grains (have bran, germ and aleurone layer); refined grains like refined sugar with high glycemic index | |
Artificial food additives | |
Aspartame and monosodium glutamate reportedly trigger inflammatory responses (particularly in those with inflammatory conditions, for example, rheumatoid arthritis | |
Sugars | |
Trans fats (found in deep fried foods, commercially baked goods, and those prepared with partially dehydrongenated oil, margarine and vegetable shortening |
In addition, in the interest of best practice, as primary nonpharmacologic practitioners, contemporary physical therapists are integrating into practice health education including initiating and supporting smoking cessation, improved sleep hygiene, and stress management [
The benefits of healthy living have no better been exemplified than in an elegant but simple study reported by Ford and colleagues [
In the interest of best practice, healthy living recommendations need to be prescribed as uniquely for their direct effects on the pathoetiology of osteoarthritis, and prescribed as aggressively as first-line medications. Although general health recommendations are important for health promotion and disease prevention generally, the tenets of healthy living need to be systematically targeted to the patient’s signs and symptoms and prescribed accordingly including long-term followup and support. Not doing so deprives the patient of evidence-informed best practice osteoarthritis management and care.
Consistent with healthy living as a first-line approach, patients’ health behaviors need to be assessed in a measurable, reproducible, and standardized manner. In addition to questionnaires and self-reports, despite their limitations, inflammatory biomarkers such as C-reactive protein may be useful to objectively measure the effects of lifestyle behavior change rather than simply as an index of cardiovascular and diabetes risk [
To address the reports of health care practitioners about lack of knowledge and confidence to effect health behavior change, they have a range of evidence-based interventions at their disposal that are not time or resource intense [
In the interest of best practice, lifestyle behaviors need to be systematically assessed in every patient and monitored across the health professions the patient is seeing. Healthy living recommendations need to be prescribed as uniquely for their direct effects on the pathoetiology of osteoarthritis as medications are, and as aggressively if first-line management is to truly reflect evidence-based practice. Although general recommendations are important for health promotion and disease prevention generally, healthy living recommendations must be systematically targeted to the patient’s signs and symptoms. In addition to integrating dietary and activity recommendations, smoking cessation, sleep hygiene, and stress reduction should be included in the interest of comprehensive effective care. Not doing so deprives the patient of best practice osteoarthritis management in relation to potential comorbidities that commonly present in this cohort.
The evidence supporting lifestyle behaviour change to address low-grade inflammation in people with osteoarthritis often with coexistent lifestyle-related risk factors and low-grade inflammatory conditions (specifically, anti-inflammatory nutritional regimens, and moderate physical activity) is unequivocal. The evidence is sufficiently compelling for related healthy living assessment and recommendations be a component of first-line best practice in the management of the signs and symptoms of people with osteoarthritis. Assessments need to include lifestyle profiles related to body mass index, waist girth, and waist-to-hip ratio; physical activity and exercise, as well as smoking, sleep patterns, and stress (as these three latter factors have also been reported to be proinflammatory). When quantified in standardized ways, these profiles can serve as clinical outcomes to assess health behavior change interventions. The health behaviour change literature has exploded over the past two decades, yet health professions report lack of confidence in effecting health behavior change in their patients, and lack of resources including time [
Studies are needed to examine the differentiating characteristics of those people with osteoarthritis who respond primarily to optimal nutrition and moderate physical activity, and those who do not. In addition, the elements of an anti-inflammatory nutrition regimen and moderate physical activity program need to be refined in terms of their prescriptive parameters, specifically, which elements should be a primary focus for which patients. Another line of studies is needed to examine the effect of such healthy lifestyle choices that increase inflammation threshold, on the need for medication and, if medication is indicated, how might its potency and dosage be reduced. The interactions among healthy lifestyle behaviors and pharmacokinetics need to be elucidated. Given that chronic systemic low-grade inflammation has been reported to be a common denominator of lifestyle-related conditions, studies are needed to establish the degree to which their risk factors and manifestations are reduced in people with chronic osteoarthritis whose first-line management includes prescribing optimal nutrition and physical activity for their anti-inflammatory effects. Furthermore, the impact of low-grade inflammation can be more far reaching than physical complaints alone, in that even healthy older adults report poorer health commensurate with level of inflammatory markers [
Based on the extant literature, exploitation of anti-inflammatory lifestyle behavior change as ‘‘first-line’’ intervention in the management of chronic osteoarthritis could well constitute best practice. Chronic low-grade inflammation that has been reported in chronic osteoarthritis is comparable to other lifestyle-related conditions supporting a common mechanism of action. Addressing chronic low-grade inflammation by focussing on lifestyle factors that contribute directly to it holds the promise of increasing a patient’s inflammatory threshold, reducing rate of disease progression, reducing weight, and maximizing health by minimizing a patient’s risk or manifestations of other lifestyle-related conditions. Even in part, such outcomes could minimize demands on physicians for short-term symptom reduction, and management of the patient’s comorbidity related to lifestyle-related conditions. ‘‘First-line’’ lifestyle interventions to address chronic low-grade inflammation provides an informed cost-effective basis for the 21st century prevention, potential reversal, and management of chronic osteoarthritis. Exploitation of such ‘‘first-line’’ intervention, however, needs to be a goal shared and supported by all healthcare team members.