SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – Moderate alcohol intake and fish consumption are the two dietary factors supported by the strongest epidemiologic evidence for a protective effect against development of rheumatoid arthritis, while sugar-sweetened sodas are associated with increased risk of the disease.

“Sugar-sweetened soft drinks are now the primary source of sugar in the American diet. This consumption has increased astronomically over the past 30 years,” Dr. Karen H. Costenbader observed at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Obesity, one consequence of America’s love affair with sugar, is a moderately potent independent risk factor for RA, according to several studies, including one carried out by Dr. Costenbader and her colleagues at Brigham and Women’s Hospital and Harvard University, Boston.

They followed nearly 220,000 women enrolled in the Nurses Health Study (NHS) and NHS II prospective cohort studies. During 4.7 million person-years of follow-up, women who were diagnosed with RA before age 55 were 45% more likely to be overweight and 65% more likely to be obese than were women without RA at that age. The association was stronger for seropositive than seronegative RA. Moreover, in an analysis that considered cumulative years of obesity as something akin to pack-years of smoking, the investigators found strong evidence of a dose effect, such that 10 cumulative years of being obese was associated with a 37% increased risk of RA by age 55 ( Ann. Rheum. Dis. 2014;73:1914-22 ).

These findings were consistent with the results of a retrospective, population-based study of Olmsted County, Minn., residents conducted by investigators at the Mayo Clinic. They found that a history of obesity was associated with a 24% increased likelihood of developing RA. The investigators calculated that obesity could account for 52% of the sharp increase in the incidence of RA seen in the county, as elsewhere, between 1985 and 2007 ( Arthritis Care Res. 2013;65:71-7 ).

The mechanism by which obesity may boost the development of RA is unknown. Speculation has focused on inflammation as the likely mediator. Visceral fat secretes proinflammatory cytokines, with resultant elevations in C-reactive protein, TNF-alpha, and other biomarkers of systemic inflammation, Dr. Costenbader said.

The importance of eating fish as a protector against developing RA is also supported by multiple epidemiologic studies. Investigators at the Karolinska Institute in Stockholm demonstrated in a study of 1,889 Swedish RA patients and 2,145 controls that eating oily fish on as few as 1-3 occasions per month was associated with a 20% reduction in the odds of developing RA ( Epidemiology 2009;20:896-901 ).

The Swedish findings were confirmed in a recent, not-yet-published analysis of women enrolled in the Nurses’ Health Study and NHS II. Dr. Costenbader and coworkers showed that eating fish at least once per month was associated with a 28% reduction in RA risk, compared with never-eaters of fish.

The evidence for a preventive effect of eating fish and a contributory role of obesity in the development of RA is sufficiently strong that these two behavioral factors have been incorporated in the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study . This is an ongoing National Institutes of Health–funded, prospective, randomized, controlled trial being conducted by Dr. Costenbader and others at Brigham and Women’s Hospital.

The PRE-RA Family Study is designed to compare the willingness to change RA-associated behaviors among first-degree relatives of RA patients after exposure to an online personalized risk-estimation tool and education program. The four behavioral factors included in the risk estimator – and targeted for change in the online risk education program – are cigarette smoking, excess body weight, low fish intake, and poor oral health.

Dr. Costenbader said “the sweet spot” for alcohol consumption in terms of reducing RA risk was 5.0-9.9 g/day – equivalent to one-half to one drink – in an analysis of incident RA cases she and her coinvestigators performed in the NHS and NHS II cohorts ( Arthritis Rheumatol. 2014;66:1998-2005 ).

In the sugar-sweetened soda study, she and her coworkers found that nurses who drank more than one serving per day had a 63% greater risk of developing seropositive RA compared with those who consumed less than one per month. Restricting the analysis to women with onset of RA after age 55, the association grew markedly stronger, with one or more soft drinks per day linked to a 2.64-fold increased risk ( Am. J. Clin. Nutr. 2014;100:959-67 ).

Lots of other dietary factors, including coffee, tea, red meat, protein, vitamins and antioxidant-rich foods, and the Mediterranean diet pattern, have been looked at by various investigators. None have panned out.

Dr. Costenbader’s research is supported by the NIH and the Arthritis Foundation. She reported having no financial conflicts.


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