The Role of Nutrition in Osteoarthritis

By Caroline Schepker, DO

Osteoarthritis (OA) is the fastest growing form of disability worldwide (1), and treatment options for symptomatic OA are fairly limited and often only provide temporary relief. Furthermore, OA has classically been considered a non-inflammatory arthritis while only rheumatologic arthritides were considered inflammatory in nature. However, recent research suggests an underlying low-grade inflammatory component to OA that may be rooted in chronic systemic inflammation and the metabolic syndrome (2,3,4). Furthermore, synovitis has recently been identified as a hallmark feature of OA. Other critical features likely involve subchondral bone as a source of inflammatory mediators, as well as the release of matrix metalloproteinases by cartilage in response to both systemic and localized cytokines and prostaglandins (5). Increased adiposity is associated with adipokine release and activation of pro-inflammatory interleukins. Hyperglycemia and high LDL cholesterol are also independently associated with systemic inflammation. These systemic metabolic derangements could possibly be playing a role in triggering pain attacks in patients with non-post-traumatic osteoarthritis.

The role of addressing systemic inflammation through lifestyle, particularly dietary modifications, dates back several thousand years to the advent of Ayurvedic and Traditional Chinese Medicine dietary practices, which have historically sought to address arthritis by eliminating foods that produce “heat” in the body and emphasize “cooling” foods. More recent research examining the effects of diet on the most inflammatory form of arthritis — rheumatoid arthritis (RA) — suggests that these age-old traditions might have had something right. There is an abundance of literature examining dietary interventions in rheumatologic diseases, given the high concordance of these conditions with gastrointestinal diseases such as IBD. Fraser et al. studied a group of RA patients who were advised to engage in “subtotal fasting” — they were allowed to consume a limited amount of vitamin and mineral supplementation, carbohydrate, and energy in the form of vegetable juice for one week. As compared with controls, this group was found to have decreased CD4+ lymphocyte activation and numbers — a process indicative of progression of RA. Their theory was that transient immunosuppression was able to suppress the pro-inflammatory process underlying RA (6). Michalsen et al. also showed clinical improvement in RA patients who underwent fasting protocols (7). Kjeldsen-Kragh et al. asked RA patients to fast for 7–10 days with partial nutrient intake of vegetable broth, herbal teas, parsley, garlic, potatoes, and juice extracts from carrots, beets, and celery. This period was followed by either one year of a 100% plant-based (vegan) diet or an omnivorous diet. The participants who followed the fast with a vegan diet demonstrated statistically significant clinical decreases in swollen and tender joints and pain, as well as blood markers of inflammation (ESR and CRP) (8).

Thomas et al. performed a literature review of the relevance of dietary interventions to OA management in 2018. This group found six modifiable nutritional factors that may be implicated in OA: adiposity/obesity, metabolic syndrome, type 2 diabetes, consumption of long-chain n-3 fatty acids, blood cholesterol levels, and vitamin K intake (9).

Adiposity and Obesity

Obesity increases axial load compression on weight bearing joints; over time, overweight and obese individuals are increasingly more likely to electively have a knee replaced than their normal-weight counterparts (10). Interestingly, higher BMI is also associated with higher risk for OA in non-weight-bearing joints as well — particularly the hand — which suggests a non-mechanical and perhaps inflammatory or biochemical etiology (11). One theory underlying the inflammatory role of fat tissue lies in adipokines — proteins secreted by adipocytes that trigger a cascade of pro-inflammatory cytokines. Leptin is a specific adipokine that is elevated in the postprandial state and is often chronically elevated in obesity. High blood levels of leptin are also independently associated with inflammation and cartilage degradation (12, 13).

Metabolic Syndrome

The metabolic syndrome is defined as the coexistence of central obesity, insulin resistance, dyslipidemia, and hypertension. The Research on Osteoarthritis/Osteoporosis Against Disability cohort (n=1384) showed increased radiographic incidence and progression of knee OA with accumulation of components of the metabolic syndrome; this was similarly observed in the Melbourne Collaborative Cohort Study (14, 15). Possible mechanisms underlying this correlation include increased systemic inflammation, higher axial compression/weight bearing secondary to increased BMI, and impaired blood flow to microvasculature in the setting of dyslipidemia and atherosclerotic disease, which may ultimately prolong and impair healing and repair from the daily wear-and-tear on bones and soft tissues of the musculoskeletal system.

Type 2 Diabetes

Impaired glucose tolerance and prolonged, chronically elevated blood sugar results in accumulation of AGEs, or advanced-glycation end products — proteins and lipids that become glycated when exposed to sugars. AGEs are believed to play a role in the pathogenesis of many degenerative diseases including atherosclerosis, chronic kidney disease, and neurodegenerative diseases. AGEs induce a pro-coagulant state, vasoconstriction, pro-inflammatory cascades, free radical formation, and lipogenesis. A German cohort study found type 2 diabetes to be an independent risk factor for severe OA, as well as a predictor for knee and/or hip replacement (16). A subsequent French study assessed patients with knee OA over 3 years; type 2 diabetes was again a statistically significant predictor of reduction of joint space width in men (17).

Dietary lipids

Interestingly, dietary lipids can make their way into the matrix and chondrocytes of articular cartilage and act as a source of inflammation — a study by Plumb et al. found high levels of pro-omega-6 fatty acids, precursors to pro-inflammatory eicosanoids, in cores of cancellous bone taken from the femoral heads of patients undergoing orthopedic surgery to address OA (18). Furthermore, in individuals with knee OA, a positive correlation has been identified between serum levels of the omega-6 polyunsaturated acid arachidonic acid and synovitis; conversely, an inverse relationship has been identified between serum levels of omega-3 docosahexaenoic acid (DHA) and patellofemoral cartilage loss as measured by MRI (19). Finally, a larger prospective study of OA patients found that higher intakes of both total fat and saturated fat were associated with increased radiographic evidence of knee joint space loss (20). The Western diet typically boasts a high ratio of omega-6 to omega-3 fatty acids, which may predispose individuals to inflammation. Arachidonic acid, a metabolite of omega-6 fatty acids, is pro-inflammatory and typically sourced from animal fats such as meats, dairy, and eggs, as well as some vegetable oils — namely safflower and sunflower oil. EPA and DHA, anti-inflammatory metabolites of omega-3 fatty acids, are predominant in walnuts, flaxseeds, and algae- or fish-based oil supplements.

Cholesterol

Dyslipidemia has long been identified as an independent risk factor for OA — backed by several epidemiologic studies (21, 22, 23). An Australian cohort of healthy middle-aged women found that, for every 1 mmol/L increase in total serum cholesterol, the adjusted odds of developing a bone marrow lesion were 1.84 (24). Statin use seems to ameliorate some of the symptoms of OA — a 10-year longitudinal study in a cohort of 16,609 participants found that increasing statin dose in dyslipidemic patients was associated with decreased clinical features of OA (25). Statin use was also found to be associated with improved imaging findings — resulting in over 50% reduction in radiographic progression of knee OA (26). It is possible that this effect could be mediated not only by the LDL-reducing effects of statins, but also by their anti-inflammatory effects; statins have been shown to reduce expression of inflammatory cytokines and exert chondroprotective effects — with atorvastatin in particular inhibiting interleukin 1B and matrix metalloproteinase 13 in vitro (27). The mechanisms underlying the interplay between serum cholesterol and OA are unclear — but cholesterol, like fatty acids, has also been found to accumulate in the articular cartilage of individuals with OA, and high LDL in particular may play a direct role in triggering synovitis and subsequent osteophyte formation (28). Statins may not be necessary; dietary and exercise interventions alone can have dramatic affects on lipid profile. Strategies include restricting saturated fat to 11% or less of total energy, generous consumption of soluble fiber, moderate consumption of soy protein (25g/daily), and a dietary foundation in plant sterols and stanols — found in virtually all whole plant-based foods. In fact, there appears to be a dose-effect relationship between plant stanols and LDL cholesterol, with 9–10g of daily stanols lowering LDL cholesterol by 18% (29).

Vitamin K

Vitamin K is involved in bone and cartilage mineralization, and is largely obtained in the diet from green leafy vegetables (vitamin K1) and bacteria (vitamin K2). Suboptimal vitamin K intake may cause decreased carboxylation of vitamin-K dependent proteins, which induce anabolic processes in bone and cartilage (30). In several longitudinal studies, individuals who were deficient in vitamin K were more likely to have articular cartilage and meniscal damage in the knees (31, 32). Only one randomized, controlled trial examining the effect of vitamin K supplementation on OA exists — and although it failed to find a beneficial effect of supplementation on progression of OA, only a small percent of the cohort was truly vitamin K deficient at baseline. Within that small group, those who achieved therapeutic blood levels demonstrated 47% less joint space narrowing at follow-up (p = 0.02)(33).

Conclusions

Osteoarthritis, which was once believed to be a pure reflection of years of mechanical wear-and-tear on joints, is in reality a complex degenerative disease that likely has roots in the underlying health of the individual. OA risk factors may be even more heavily modifiable than many clinicians consider or address with their patients. Chronic, low grade systemic inflammation from diet and adiposity; suboptimal blood flow secondary to increased viscosity from hyperglycemia and hypercholesterolemia; subtle underlying nutritional deficiencies that hamper optimization of growth and repair mechanisms; research has only begun to scratch the surface of the many factors at play. However, when taken as a whole, many of these modifiable risk factors can be addressed in the same way: by prioritizing a whole foods and plant-rich diet — one that is relatively low in energy density to support normalization of weight, high in fiber and plant sterols/stanols to promote healthy blood lipid levels, and high in leafy greens and omega 3 fatty acids to support optimal micro- and macronutrient intake. In 2015, a six-week, prospective, randomized study of 37 patients aged 19–70 with symptomatic OA found statistically significant improvements in self-reported energy, physical functioning, joint mobility, and pain in the group randomized to a whole-foods plant-based diet as compared with participants who ate their usual diets (34). As we progress in our understanding of the complex underlying biochemical and endocrinological underpinnings of this disease, we just may come to appreciate the efficacy of the simplest of approaches to symptom management and the slowing of disease progression.

References:

(1) Conaghan PG, Porcheret M, Kingsbury SR et al. Impact and therapy of osteoarthritis: the Arthritis Care OA Nation 2012 survey. Clin Rheumatol 2015; 3:1581.

(2) Sturmer T, Brenner H, Koenig W, Gunther KP. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Annals of the Rheumatic Diseases 2004; 63:200–205.

(3) Zhuo Q, Yang W, Chen J, Wang Y. Metabolic syndrome meets osteoarthritis. Nature Reviews: Rheumatology 2012; 8:729–737.

(4) Engstrom G, Gerhardsson de Verdier M, Rollof J et al. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis: a population-based cohort study. Osteoarthritis and Cartilage 2009; 17:168–173.

(5) Berenbaum F. Osteoarthritis as an inflammatory disease. Osteoarthritis and Cartilage 2013; 21:16–21.

(6) Fraser D, Thoen J, Reseland J et al. Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation. Clin Rheumatol 1999; 18:394–401.

(7) Michalsen A, Riegert M, Ludtke R et al. Mediterranean diet or extended fasting’s influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern Med 2005; 5:22.

(8) Kjeldsen-Kragh J, Borchgrevink C, Laerum E et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet 1991; 338:899–902.

(9) Thomas S, Browne H, Mobasheri A et al. What is the evidence for a role for diet and nutrition in osteoarthritis? Rheumatology 2018; 57:iv61-iv74.

(10) Leyland KM, Judge A, Javaid MK et al. Obesity and the relative risk of knee replacement surgery in patients with knee osteoarthritis: a prospective cohort study. Arthritis Rheumatol 2016; 68:817–25.

(11) Yusuf E, Nelissen RG, Ioan-Facsinay A et al. Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann Rheum Dis 2010; 69:761–765.

(12) Hui W, Litherland GJ, Elias MS et al. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann Rheum Dis 2012; 71: 455–462.

(13) Scotece M, Mobasheri A. Leptin in osteoarthritis: focus on articular cartilage and chondrocytes. Life Sci 2015; 140: 75–78.

(14) Yoshimura N, Muraki S, Oka H et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of recurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage 2012; 20:1217–1226.

(15) Monira Hussain S, Wang Y, Cicuttini FM et al. Incidence of total knee and hip replacement for osteoarthritis in relation to the metabolic syndrome and its components: a prospective cohort study. Semin Arthritis Rheum 2014; 43: 429–436.

(16) Schett G, Kleyer A, Perricone C et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care 2013; 36: 403–409.

(17) Eymard F, Parsons C, Edwards MH et al. Diabetes is a risk factor for knee osteoarthritis progression. Osteoarthritis Cartilage 2015; 23: 851–859.

(18) Plumb MS, Aspden RM. High levels of fat and n-6 fatty acids in cancellous bone in osteoarthritis. Lipids Health Dis 2004; 3:12.

(19) Baker KR, Matthan NR, Lichtenstein AH et al. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis of the knee: the MOST study. Osteoarthritis Cartilage 2012; 20: 382–387.

(20) Lu B, Driban J, Xu C et al. Dietary fat and radiographic progression of knee osteoarthritis: data from the Osteoarthritis Initiative. Arthritis Care Res 2017; 69: 368–375.

(21) Hart DJ, Doyle DV, Spector TD. Association between metabolic factors and knee osteoarthritis in women: the Chingford Study. J Rheumatol 1995; 22: 1118–1123.

(22) Sturmer T, Sun Y, Sauerland S et al. Serum cholesterol and osteoarthritis: The baseline examination of the Ulm Osteoarthritis Study. J Rheumatol 1998; 25: 1827–1832.

(23) Addimanda O, Mancarella L, Dolzani P et al. Clinical associations in patients with hand osteoarthritis. Scand J Rheumatol 2012; 41: 310–313.

(24) Davies-Tuck M, Hanna F, Davis SR et al. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women — a prospective cohort study. Arthritis Res Ther 2009; 11: R181.

(25) Kadam UT, Blagojevic M, Belcher J. Statin use and clinical osteoarthritis in the general population: a longitudinal study. J Gen Intern Med 2013; 28: 943–949.

(26) Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis 2012; 71: 642–647.

(27) Simopolou T, Malizos KN, Poultsides L, et al. Protective effect of atorvastatin in cultured osteoarthritic chondrocytes. J Orthop Res 2010; 28: 110–115.

(28) Cillero-Pastor B, Eijkel G, Kiss A et al. Time-of-flight secondary ion mass spectrometry-based molecular distribution distinguishing healthy and osteoarthritic human cartilage. Anal Chem 2012; 84: 8909–8916.

(29) Laitinen K, Gylling H. Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence. Lipids Health Dis 2012; 11: 140.

(30) Beckner KL. Vitamin K dependent carboxylation. Vitam Horm 2008; 78: 131–156.

(31) Shea MK, Kritchevsky SB, Hsu FC et al. The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging, and Body Composition Study. Osteoarthritis Cartilage 2015; 23: 370–378.

(32) Misra D, Booth SL, Tolstykh I et al. Vitamin K deficiency is associated with incident knee osteoarthritis. Am J Med 2013; 126: 243–248.

(33) Neogi T, Fleson DT, Sarno R et al. Vitamin K and hand osteoarthritis: results from a randomized controlled trial. Ann Rheum Dis 2008; 67: 1570–1573.

(34) Clinton C, O’Brien S, Law J et al. Whole-foods, plant-based diet alleviates the symptoms of osteoarthritis. Arthritis 2015; 2015: 708152.

Caroline Schepker, DO is a PGY3 in PM&R at NYP-Columbia/Cornell who is interested in musculoskeletal and integrative medicine.