Two new studies presented today at the European League Against Rheumatism Annual Congress (EULAR 2014) have helped clarify the relationship between the dietary intake of monounsaturated fatty acids and cholesterol with disease activity in rheumatoid arthritis (RA) and osteoarthritis (OA) respectively.
In the TOMORROW study, daily intake of monounsaturated fatty acids as a component of the Mediterranean diet has been shown to be an independent predictor of remission in patients with RA; monounsaturated fatty acids might therefore be suppressing disease activity.1
In another study, using an experimental animal model of OA, accumulation of LDL-cholesterol resulted in an increase in synovial thickening and ectopic bone formation, with excessive cholesterol levels shifting the balance towards increased cartilage damage.2
Researchers have been exploring the link between diet and different types of arthritis since the 1930's.3 While the relationship between diet and arthritis is certainly complex, these two studies have highlighted the importance of addressing dietary intake of monounsaturated fatty acids and cholesterol when treating patients with RA and OA respectively.
Dietary intake of monounsaturated fatty acids independently predicts remission in RA Using the RA disease activity score calculator DAS28-ESR to categorise patients as having active disease or being in remission, dietary intake of monounsaturated fatty acids was shown to be an independent predictor of remission in patients with RA (Odds: 0.51; 95% CI = 0.25 .02, p = 0.057). The intake of monounsaturated fatty acids and of Mediterranean diet components was significantly lower in the RA than in the control group (p = 0.003).1
The ratio of monounsaturated fatty acids to saturated fatty acids was significantly lower in patients with RA with high disease activity vs. those patients in remission and those with low disease activity (p = 0.033, 0.010, 0.047, respectively).
"We now have a much better understanding of the relationship between disease activity in patients with RA and the Mediterranean diet based on the findings from our 10-year-prospective cohort study TOMORROW," said lead author Mr. Yoshinari Matsumoto of the Department of Medical Nutrition, Graduate School of Human Life Science, Osaka City University, Japan.
A previous study had shown that, by adjusting to a Mediterranean diet, patients with RA could obtain a reduction in inflammatory activity, an increase in physical function, and improved vitality.4 However, this is the first time the key elements within a Mediterranean diet involved in these beneficial effects have been assessed.
"Confirming that daily intake of monounsaturated fatty acids, as a component of the Mediterranean diet, is an independent predictor of remission in patients with RA suggests that monounsaturated fatty acids might actually be suppressing disease activity," Mr. Matsumoto concluded.
In this study, data was collected from 208 consecutive patients with RA and 205 age- and gender-matched healthy volunteers. Daily food and nutrient intake status were assessed using a brief, self-administered diet history questionnaire and Mediterranean diet scores were calculated from reference results from the control group. Cholesterol influences disease activity in OA
To further investigate the link between cholesterol and OA pathology, ApoE deficient mice (a model for extremely high systemic LDL cholesterol levels) received a normal or cholesterol-rich diet for 54 days; wild type mice were used as controls. At day 18, experimental OA was induced by intra-articular injection of collagenase.2
While no differences between the two groups of mice fed a normal diet were found at the early time point of the study (day 28), by day 54 (end-point OA) the ApoE deficient mice showed a strong increase of ectopic bone formation, mainly at the medial collateral ligament (5.4-fold increase; p<0.001) compared to the control mice.
No significant differences in cartilage damage were found between the two groups of mice that were fed a normal diet. However, a slight increase in synovial thickening was found in the ApoE deficient mice compared to the control mice (1.9 vs. 1.1 respectively; p<0.05), suggesting an activated status of synovial lining cells.
The ApoE deficient mice on a normal diet had shown markedly higher LDL levels than the control mice (8.90 mmol/L and 0.40 mmol/L, respectively; p<0.001).
A second analysis investigated the impact of a cholesterol-rich diet on joint pathology after induction of OA was investigated. In contrast to when the two groups of mice were fed a normal diet, the cholesterol-rich diet increased LDL levels even further in the ApoE deficient mice: a 2.1-fold increase compared to ApoE deficient mice on a normal diet (p<0.001).
Adding a cholesterol-rich diet to the ApoE deficient mice resulted in significant histological differences becoming apparent at day 28. Synovial thickening was increased four times (p<0.001), and also ectopic bone formation in the medial collateral ligament was strongly increased at this early time point (2.7-fold increase; p<0.01).
Interestingly, the addition of a cholesterol-rich diet to ApoE deficient mice did not enhance ectopic bone formation at day 54. In fact, it decreased by 40% in the medial collateral ligament compared to those ApoE deficient mice fed a normal diet. However, cartilage damage at the medial side of the femoral condyle was strongly increased compared to the ApoE deficient mice receiving a normal diet (1.6-fold increase; p<0.05).
According to lead author, Dr. Wouter de Munter of the Department of Experimental Rheumatology, Radboud University Medical Centre, Nijmegen, Netherlands, a relationship between OA and metabolic syndrome, the medical term for a combination of diabetes, high blood pressure and obesity, has long been established.
"With one of the characteristics of metabolic syndrome being increased cholesterol levels, research has been ongoing into clarifying the relationship between cholesterol and OA pathology," explained Dr. de Munter. In our earlier study using an animal model of experimental arthritis, LDL accumulation in LDL receptor deficient mice had resulted in increased ectopic bone formation.5 "This new study has provided a lot more evidence that cholesterol plays an important role in determining disease activity in OA," Dr. de Munter concluded.
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More information: Abstract Numbers: OP0010-HPR and OP0129
1 Matsumoto Y, Sugioka Y, Tada M, et al. Intake of monounsaturated fatty acids as components of a Mediterranean diet suppresses Rheumatoid Arthritis disease activity – the TOMORROW study. EULAR 2014; Paris, Abstract OP0010-HPR
2 De Munter W, van den Bosch MH, Slöetjes AW, et al. LDL cholesterol-accumulation during experimental OA leads to increased synovial thickening and ectopic bone formation, while excessive cholesterol levels shift the balance towards cartilage destruction. EULAR 2014; Paris, Abstract OP0129
3 Koch C. Nutrition & Rheumatoid Arthritis. Johns Hopkins Arthritis Center. www.hopkinsarthritis.org/patient-corner/disease-management/rheumatoid-arthrtis-nutrition/ [Accessed 03/06/2014]
4 Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003; 62 (3): 208-14
5 de Munter W, Blom AB, Helsen MM, et al. Cholesterol accumulation caused by low density lipoprotein receptor deficiency or a cholesterol-rich diet results in ectopic bone formation