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Diet and Rheumatoid Arthritis Development

20 marzo, 2015

Diet and Rheumatoid Arthritis Development

What Does the Evidence Say?

Daniela Di Giuseppe, Alicja Wolk

Int J Clin Rheumatol. 2014;9(2):169-182.

Abstract and Introduction

Abstract

Rheumatoid arthritis (RA), a chronic autoimmune disease, is related to both genetic and environmental factors. Among environmental factors, only smoking can be considered as an established risk factor for RA, while mixed results have been observed regarding other potential risk factors. Diet has been evaluated in several studies for its role in the management of established RA, while fewer studies have examined diet in relation to the development of RA. This review summarizes the published evidence on the association between diet and RA risk, with attention to specific foods and their nutrient content. Results stratified by types of RA are also presented.

Introduction

Rheumatoid arthritis (RA), an inflammatory autoimmune disease, is characterized by chronic, destructive, debilitating arthritis of the joints. RA affects approximately 1% of the adult population,[1] and is caused by both genetic and environmental factors.[2]
Among environmental factors, diet may play a fundamental role in the prevention of some chronic diseases owing to its potential as a modifiable risk factor. For this reason, it is of primary importance to study the role of diet in the etiology of RA in order to identify foods and dietary patterns that could help in reducing the risk of RA, as well as dietary factors that, on the contrary, may increase the risk. Diet has been evaluated in several studies for its role in the management of established RA,[3] while fewer studies have examined diet in relation to the development of RA.
In this review, the authors will summarize available epidemiological evidence on the relationship between diet and risk of RA, with attention to specific foods ( ) and their nutrient content ( ).

Table 1.  Summary of studies reporting measures of association between food consumptions and rheumatoid arthritis.

Study name or location Publication year Design Number of cases vs controls/cohort size Direction of association Rheumatoid arthritis subtypes Ref.
Fish
Greece 1991 Hospital-based case–control 168/137 No association [4]
Greece 1999 Hospital-based case–control 145/188 No association [5]
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
EIRA 2009 Population-based case–control 1889/2145 Inverse ACPA positive: inverse
ACPA negative: no association
RF positive: inverse
RF negative: no association
[7]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
SMC 2013 Prospective cohort 205/32,232 Inverse [10]
Meat
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Dairy products
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
IWHS 2004 Prospective cohort 152/29,368 Inverse [12]
Fruit
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Vegetables
Greece 1999 Hospital-based case–control 145/188 Inverse [5]
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Olive oil
Greece 1991 Hospital-based case–control 168/137 Inverse [4]
Greece 1999 Hospital-based case–control 145/188 Inverse [5]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Coffee
Denmark 2006 Population-based case–control 515/769 Positive Anti-CCP positive: positive
Anti-CCP negative: no association
[15]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
Finland 2000 Prospective cohort 126/18,981 Positive [16]
BWHS 2001 Prospective cohort 71/64,000 Positive only for decaffeinated coffee [17]
IWHS 2002 Prospective cohort 158/31,336 Positive only for decaffeinated coffee RF positive: positive
RF negative: no association
[18]
NHS 2003 Prospective cohort 480/83,124 No association RF positive: positive [19]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Tea
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
BWHS 2001 Prospective cohort 71/64,000 Positive [17]
IWHS 2002 Prospective cohort 158/31,336 Inverse RF positive: inverse
RF negative: no association
[18]
NHS 2003 Prospective cohort 480/83,124 No association RF positive: no association [19]
Alcohol
Leiden, The Netherlands 1990 Hospital-based case–control 135/378 Inverse [20]
King County, WA, USA 1994 Population-based case–control 349/1457 No association [21]
Denmark 2006 Population-based case–control 515/769 No association Anti-CCP positive: inverse
Anti-CCP negative: no association
[15]
EIRA 2009 Population-based case–control 1204/871 Inverse ACPA positive: inverse
ACPA negative: inverse
[22]
CACORA 2009 Population-based case–control 444/533 Inverse ACPA positive: inverse
ACPA negative: no association
[22]
Sheffield, UK 2010 Population-based case–control 873/1004 Inverse Anti-CCP positive: inverse
Anti-CCP negative: inverse
[23]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
Malmö Diet and Cancer Study 2013 Nested case–control 172/688 Inverse RF positive: inverse
RF negative: no association
[24]
Finland 2000 Prospective cohort 126/18,981 No association [16]
IWHS 2002 Prospective cohort 158/31,336 No association [25]
SMC 2012 Prospective cohort 197/34,141 Inverse [26]

RF: Rheumatoid factor.

Table 2.  Summary of studies reporting measures of association between nutrients intake and rheumatoid arthritis.

Study name or location Publication year Design Number of cases vs controls/cohort size Direction of association Comments Ref.
Long-chain n-3 polyunsaturated fatty acids
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
DCH 2005 Prospective cohort 69/57,053 No association [8]
SMC 2013 Prospective cohort 205/32,232 Inverse [10]
Vitamin D
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
IWHS 2004 Prospective cohort 152/29,368 Inverse [12]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2008 Prospective cohort 722/186,389 No association [27]
NHS and NHS II 2012 Prospective cohort 800/119,173 No association Intake during adolescence [28]
Iron
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Calcium
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
IWHS 2004 Prospective cohort 152/29,368 No association [12]
Selenium
Finland 1994 Nested case–control 14/28 Inverse [29]
Finland 2000 Nested case–control 122/357 Inverse RF positive: no association
RF negative: inverse
[30]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
Protein
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Vitamin C
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
EPIC-Norfolk 2005 Nested case–control 88/176 Inverse [31]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS and NHS II 2010 Prospective cohort 787/18,4643 No association [32]
α-tocopherol (vitamin E)
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
Finland 1994 Nested case–control 14/28 Inverse [29]
Finland 2000 Nested case–control 122/357 Inverse RF positive: no association
RF negative: no association
[30]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
The Women’s Health Study 2008 Randomized, double-blind, placebo-controlled trial 106/39,144 No association Seropositive RA: no association
Seronegative RA: no association
[33]
Carotenoids (α-carotene)
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (β-carotene)
Finland 1994 Nested case–control 14/28 Inverse [29]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
DCH 2005 Prospective cohort 69/57,053 No association [8]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (β-crypthoxantin)
EPIC-Norfolk 2005 Nested case–control 88/176 Inverse [31]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (lycopene)
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (lutein/zeaxanthin)
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (retinol; vitamin A)
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
Finland 1994 Nested case–control 14/28 No association [29]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
DCH 2005 Prospective cohort 69/57 053 No association [8]

RA: Rheumatoid arthritis; RF: Rheumatoid factor.

Results from studies in which inflammatory polyarthritis was used as proxy of RA were also included.[11,13,31]

Foods of Animal Origin

As part of diet, foods from both animal and plant origin have been investigated, as well as different beverages. The authors will first present published results for foods and nutrients from animal sources, including fish, meat and dairy products.

Fish

Fish consumption is considered protective against several chronic diseases, including cancer[34–36] and cardiovascular diseases.[37,38] Seven observational studies have analyzed the association between fish consumption and RA, and results are mixed.[4–10] Among the four case–control studies, two hospital-based case–control studies conducted in Greece by the same research group have reported a lack of association between fish consumption and RA.[4,5] A population-based case–control study conducted in western Washington (DC, USA) found no association between total fish (including shellfish) consumption and RA, while observing a 43% reduced risk (odds ratio [OR]: 0.57; 95% CI 0.35–0.93) of RA among women who consumed two or more servings of broiled or baked fish per week.[6] The inverse association was even stronger for rheumatoid factor (RF)-positive RA risk (OR: 0.32; 95% CI 0.14–0.72). The EIRA study, a large population-based case–control study conducted in Sweden, found a modest decrease in risk of total RA and type-specific RA – including RF positive and negative, and ACPA positive and negative – associated with consumption of oily fish (OR: 0.8; 95% CI: 0.6–1.0, for one to seven servings/per week vs never/seldom).[7]
In addition, the three prospective cohort studies presented mixed results. An inverse association was observed in the DCH cohort in Denmark between oily fish and RA (relative risk [RR]: 0.51; 95% CI 0.25–1.03), while the association was positive between medium oily fish and RA (RR: 2.74; 95% CI 1.39–5.42).[8] The researchers did not draw any conclusion regarding these discrepant results owing to the very limited number of cases (n = 69) identified in their large cohort (n = 56,691) during an average follow-up time of 5.3 years. Results from the NHS, a prospective cohort study in which nurses were asked about dietary intake every 4 years from 1980 to 1998, did not show an association between total fish and RA.[9] The SMC study analyzed the long-term consumption of fish and observed that women with consistent consumption of one or more servings of fish per week for a period of more than 10 years had a 30% decreased risk of RA (RR: 0.71; 95% CI: 0.18–1.04).[10]
As shown above, only one study analyzed the method of preparation of fish.[6] The difference in results between broiled or baked fish compared with fried fish, for which no association was observed, suggests that the method of preparation may influence the beneficial effects of fish.
Long-chain n-3 Polyunsaturated Fatty Acids. The observed inverse association between fish consumption and RA risk has been attributed to their content of long-chain n-3 polyunsaturated fatty acids (PUFAs). The n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid are metabolized to competitive inhibitors of n-6 PUFAs (prostaglandins and leukotrienes) and suppress the production of the inflammatory cytokines, such as TNF-α and IL-1β,[39] involved in RA development. However, only three studies have directly examined these nutrients. The case–control study among women of western Washington (DC, USA) found no association between intake of long-chain n-3 PUFAs and total RA, while they observed an inverse association with RF-positive RA.[6] The study conducted in the DCH cohort (based on only 69 cases) also found no association with RA.[8] Results from the SMC showed a threshold effect of long-chain n-3 PUFAs on RA risk: an intake of more than 0.21 g per day (first quintile of the distribution in the study population) was associated with a decrease in RA risk of 35% (RR: 0.65; 95% CI: 0.48–0.90).[10] Moreover, this study showed that a consistent long-term intake over more than 10 years of more than 0.21 g per day was associated with a 52% decrease in RA risk (RR: 0.48; 95% CI: 0.33–0.71).
Vitamin D. Fish is also the main dietary source of vitamin D. Some studies have shown that vitamin D may reduce the development of autoimmune diseases.[40,41] The first study that examined vitamin D in relation to RA risk was conducted in the prospective IWHS and showed an inverse association between vitamin D intake and RA (RR: 0.67; 95% CI: 0.44–1.00, for a daily intake of vitamin D of ≥467.7 vs <221.4 IU per day).[12] The association was stronger for vitamin D from supplements (RR: 0.66; 95% CI: 0.43–1.00) than dietary vitamin D (RR: 0.72; 95% CI: 0.46–1.14). However, other studies were not able to confirm these findings. No associations were observed for dietary vitamin D intake in the DCH cohort,[8] in the NHS nor in the NHS II cohort, a second prospective cohort study of younger nurses aged 25–42 years in 1989, who completed nutritional questionnaires in 1991, 1995 and 2001.[27] By contrast, an increased risk was observed for vitamin D supplements in the NHS II cohort.[27] No association was observed between dietary intake of vitamin D during adolescence and RA later in life in the NHS or NHS II.[28] A nested case–control study on inflammatory polyarthritis within the EPIC-Norfolk study reported a weak nonstatistically significant positive association between dietary intake of vitamin D and inflammatory polyarthritis.[13]
Selenium. Fish is also rich in selenium. Adequate levels of selenium are important for immunity, and selenium is also involved in regulating excessive immune responses and chronic inflammation.[42] No association was observed between selenium intake and inflammatory polyarthritis risk in the EPIC-Norfolk study.[13] Two nested case–control studies conducted in Finland analyzed the serum concentrations of selenium in men and women with and without RA.[29,30] An elevated risk of RA was observed for low levels of selenium, but the association was not statistically significant.
Contaminants. Fish also contains persistent organic pollutants, such as polychlorinated biphenyls and methyl mercury, that could play a role in developing RA.[43] However, no studies have analyzed the influence of these contaminants on the risk of RA.

Meat

Meat consumption is an important dietary source of protein and essential nutrients including iron, zinc and vitamin B12. However, there is accumulating evidence that red meat consumption increases the risk of cardiovascular diseases[44,45] and colon cancer.[46,47] Ecological studies have shown that the prevalence of RA is also higher in countries with higher consumption of red meat.[48]
However, analytical epidemiological studies have reported a lack of association with RA. A case–control study of women conducted in Washington (DC, USA) showed no association between total meat consumption and risk of RA,[6] as well as the study conducted in the Diet, Cancer and Health cohort that found no association between red meat and total meat with the risk of RA.[8] Meat intake was extensively analyzed in the NHS, where total meat, red meat and poultry were not associated with the development of RA.[9]
However, another nested case–control study found an increased risk of inflammatory polyarthritis with high intake of red meat (OR: 1.9; 95% CI: 0.9–4.0, for >58 vs <25.5 g/day) and red meat combined with other meat products (OR: 2.3: 95% CI: 1.1–4.9, for >87.8 vs <49 g/day).[11]

Proteins

Studies have shown that low-protein diets may improve RA symptoms.[49–51] In line with this, the EPIC-Norfolk study observed a threefold increased inflammatory polyarthritis risk for high levels of protein intake (OR: 2.9; 95% CI: 1.1–7.5, for >75.3 vs <62.4 g/day).[11] By contrast, a case–control study of women in Washington (DC, USA) reported that percentage of calories from protein was inversely associated with risk of RA (OR: 0.65; 95% CI 0.46–0.94, for >17.9 vs ≤14.1% of energy per day).[6] The association with protein was even stronger for RF-positive RA (RR: 0.52; 95% CI: 0.32–0.86). A stratified analysis of protein intake by animal or vegetable source in the prospective NHS did not find any association.[9]

Iron

Dietary iron intake has been linked with increased risk of inflammation;[52] however, results from epidemiological studies on the association of dietary iron intake and risk of RA have shown no associations.[6,8,9,11]
Dairy Products. Dairy products is a broad term used to indicate milk and products derived from milk, including yogurt, cheese and butter. Dairy products have a high content of calcium, magnesium, vitamin D, and whey proteins. Some dairy products, such as cheese, cream and butter also have a high fat content that may offset any benefits of increased intake of calcium or other potentially beneficial dairy components.
There are only two studies examining dairy product consumption in relation to RA risk, and their results are not consistent. The case–control study conducted in Washington (DC, USA) showed no association between dairy products and milk beverages and risk of RA.[6] By contrast, the IWHS prospective cohort reported an inverse association between total milk products (including skim milk, whole milk, ice cream, yogurt, cottage cheese, cream cheese, and other cheese) and risk of RA (RR: 0.66; 95% CI: 0.42–1.01, for ≥68 vs 1–35 servings per month).[12] In addition, the use of butter was reported to decrease the risk of RA, while no associations were found between the consumption of other individual dairy products and RA. Neither of the two studies observed any association with calcium intake.[6,12] Regarding inflammatory polyarthritis, the nested case–control study within the EPIC-Norfolk cohort found an increased risk associated with dairy product consumption (OR: 1.9; 95% CI: 0.9–4.2, for >260 vs <153 g/day).[11]
Thus, in summary, no conclusions can be made, owing to a very limited number of studies and mixed results.

Foods of Plant Origin

Studies regarding consumption of foods of plant origin in relation to RA risk are also limited.

Fruit & Vegetables

Fruits and vegetables play an important role in diet owing to their protective action against several chronic diseases[53,54] – from cancer[55] to cardiovascular diseases.[56] Since cardiovascular diseases may have an inflammatory response similar to RA,[57] fruits and vegetables could also prevent the development of RA, especially thanks to their high content of antioxidant nutrients.
Studies on the association between fruits and vegetables and RA are limited, and results from case–control and prospective studies are not concordant. A case–control study conducted in Washington (DC, USA) found no association between fruit and vegetable consumption and RA risk.[6] However, a more recent case–control study in Greece found an inverse association between cooked vegetables and RA (OR: 0.39; 95% CI: 0.20–0.77, for >85 vs <20 servings per month), but not for raw vegetables.[5] Among prospective studies, an inverse association, although not statistically significant, was observed in the IWHS between fruit (RR: 0.72; 95% CI: 0.46–1.12, for >83 vs <52 servings per month) and vegetable (RR: 0.74; 95% CI: 0.48–1.14 for >97 vs <60 servings per month) consumption and RA.[14] Among fruits, oranges and grapefruit juice consumption showed the lowest relative risks, while among vegetables, cruciferous vegetable consumption was associated with the lowest risk. No associations with fruits or vegetables were observed in the DCH cohort.[8]
In line with the Iowa cohort study, the EPIC-Norfolk study showed that a low intake of fruits and vegetables (OR: 1.9; 95% CI: 1.0–4.0, for <167 vs >275 g/day) was associated with increased risk of inflammatory polyarthritis.[13]
Antioxidants. Fruits and vegetables are rich in antioxidants that may protect against oxidative stress. Products of free radical oxidation are present in the synovial fluid of patients with RA, indicating a role of free radicals and oxidative stress in the RA inflammation process.[58,59]
Among the four studies examining associations between antioxidants and RA, only one prospective study observed an inverse association. Several antioxidants were examined in the IWHS, where inverse associations were observed for vitamin C and β-cryptoxanthin (carotenoid) with RA, while no associations were found for vitamin E, or other specific carotenoids (α- and β-carotene, lycopene and lutein/zeaxanthin) and total carotenoids.[14] No association was observed in the DCH cohort[8] or in the NHS and NHS II[32]with antioxidant (vitamin A, C and E, α- and β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) intake from foods and supplements.
No association was observed in the case–control study conducted in Washington (DC, USA) between vitamins A, C and E and RA risk.[6] The EPIC-Norfolk study reported that low intake of vitamin C (OR: 3.3; 95% CI: 1.4–7.9, for <55.7 vs >94.9 mg/day) was associated with increased risk of inflammatory polyarthritis,[13] while the intake of vitamin E, β-carotene, and retinol were not associated with inflammatory polyarthritis. A subsequent study based on the new cases arising from the same cohort, confirmed the inverse association between vitamin C and inflammatory polyarthritis, and also showed a decreased risk associated with intake of β-cryptoxanthin.[31]
The association between antioxidants and RA was also examined using serum antioxidant concentrations in three studies. Two nested case–control study conducted in Finland observed an elevated risk of RA for low levels of serum α-tocopherol, and β-carotene, but none of the associations were statistically significant.[29,30] A case–control study in Washington County (MD, USA) analyzed the difference in serum concentration of α-tocopherol and β-carotene between RA cases and controls, finding a statistically significant decrease only for β-carotene.[60]
A randomized, double-blind, placebo-controlled trial conducted in USA, The Women’s Health Study, also evaluated vitamin E supplementation and found no association with RA.[33]

Cereals & Legumes

Consumption of whole-grain cereals has been shown to reduce levels of inflammatory markers (C-reactive protein and IL-6).[61] In addition, legumes have been found to decrease levels of inflammatory biomarkers (high-sensitive C-reactive protein, TNF-α and IL-6).[62] However, only one case–control study has analyzed the association of high-fiber cereals with RA and observed no association,[6] while no studies have analyzed the association of legume consumption with RA.

Olive Oil

Olive oil is a major component of the Mediterranean diet and is considered to be associated with many health benefits.[63] The health-related effects of olive oil are attributed to its richness in oleic acid and natural antioxidants.[64] Oleic acid has been reported to have modulatory effects in a wide variety of physiological functions, and a beneficial effect on cancer, autoimmune and inflammatory diseases.[65] Oleic acid is a n-9 monounsaturated fatty acid that is converted to 8,9,11-eicosatrienoic acid under restriction of n-6 fatty acids.[66] Oleic acid and its metabolite 8,9,11-eicosatrienoic acid may have an anti-inflammatory effect with a mechanism similar to fish oil.[5]
However, results from epidemiological studies are inconclusive. Two hospital-based case–control studies conducted in Greece found an inverse association between high consumption of olive oil and risk of RA (OR: 0.39; 95% CI: 0.19–0.82, for high vs low).[4,5] However, this finding was not confirmed in the prospective DCH cohort.[8]

Beverages

Coffee

Coffee and tea are two of the most consumed beverages in the world. The first study on coffee and RA was conducted in Finland,[16] where the association between coffee and RA was examined in a prospective cohort. The researchers found an increase in RA risk associated with a high intake of coffee (RR: 2.20; 95% CI: 1.13–4.27, for ≥four vs ≤three cups per day). However, the three following US prospective studies failed to replicate this result. The BWHS,[17] the IWHS[18] and the NHS[19] reported no association with RA for total or caffeinated coffee intake. A lack of association was also observed in the Danish DCH cohort with RA[8] and in the EPIC-Norfolk nested case–control study with inflammatory polyarthritis.[11]
However, a matched case–control study conducted in Denmark among men and women reported an increased RA risk associated with high coffee consumption (OR: 2.33; 95% CI: 1.40–3.87, for >ten vs zero cups per day).[15] This association was present among anti-CCP-positive cases, but not among anti-CCP-negative RA cases. Moreover, when the analysis was stratified by shared epitope carrier status, the risk increased only among shared epitope heterozygotes and homozygotes, but not among noncarriers.[67]

Decaffeinated Coffee

It has been hypothesized that solvents used in the decaffeination process of coffee beans may play a role in the development of RA.[68] Observational studies seem to confirm this hypothesis. Indeed, the BWHS reported a positive association for decaffeinated coffee (OR: 3.9; 95% CI: 1.8–8.3, for ≥one cup per day vs <one cup per week).[17] Similar results have been observed in the IWHS, which reported an increased risk of RA for decaffeinated coffee (RR for ≥four cups per day vs none: 2.44; 95% CI: 1.52–3.89).[18] However, the NHS found no association.[19]

Tea

It is hypothesized that tea has both antioxidative and antiinflammatory properties,[69] but results from observational studies on RA are mixed. The IWHS observed a decreased risk of RA with high consumption of tea (RR: 0.35; 95% CI: 0.13–0.97, for three cups per day vs none).[18] The NHS found no association with tea consumption.[19] In addition, no association was observed with inflammatory polyarthritis risk in the EPIC-Norfolk study.[11] In contrast to the hypothesis, the BWHS found a positive association between tea consumption and RA (OR: 2.1; 95% CI: 1.0–4.2, for ≥one cup per day vs <one cup per week).[17]

Alcohol

Long-term consumption of alcohol in moderate amounts may affect immune function and could downregulate production of proinflammatory molecules involved in the development of RA.[70–72]
Among dietary factors, alcohol has been the most studied in association with RA. The first epidemiological study to analyze a possible association between alcohol consumption and RA was a hospital based case–control study among women in The Netherlands.[20] Women who drank three or more servings of alcohol per day had a 69% reduced risk of RA compared with women who did not drink (OR: 0.31; 95% CI: 0.13–0.74). However, subsequent studies did not observe any association between alcohol and RA. A case–control study from Washington (DC, USA) considering lifetime average alcohol consumption observed no association among pre- or post-menopausal women.[21] In addition, a frequency-matched case–control study in Denmark found no association between alcohol consumption and RA in both men and women, but found a decreased risk of anti-CCP-positive RA among subjects with an alcohol consumption of more than 15 drinks per week compared with never drinkers (OR: 0.60; 95% CI: 0.35–1.04).[8] Moreover, they showed that shared epitope homozygotes reporting no alcohol consumption had a higher risk of anti-CCP-positive RA compared with noncarriers who consumed one to ten alcoholic drinks per week, suggesting a strong gene–environment interaction.[67] The EPIC-Norfolk nested case–control study reported no association between alcohol intake and inflammatory polyarthritis.[11] In addition, two prospective studies, conducted in Finland and the IWHS cohort observed no association.[16,25] The IWHS analyzed specific types of alcoholic beverages (beer, red wine, white wine and liquor), and found no association by type.
In 2008, the Epidemiological Investigation of RA (EIRA) group examined the association of alcohol consumption with RA in both their case–control study and in the Danish CACORA.[22] The researchers observed an inverse association with RA in both EIRA (OR: 0.5; 95% CI: 0.4–0.6) and CACORA (OR: 0.6; 95% CI: 0.4–0.9) for high alcohol consumption (amount not specified) compared with nondrinkers. The inverse association was also present for anti-CCP-positive RA, while the association with anti-CCP-negative RA was inverse in only the EIRA study, but not in CACORA.
All the following studies found an inverse association as well. A case–control study conducted in Sheffield (UK) demonstrated a four-times higher RA risk among never drinkers compared with those who drank more than 10 days per month (OR: 4.17; 95% CI: 3.01–5.77).[23] This study also reported an inverse association between alcohol and anti-CCP-positive and -negative RA, and also with measure of disease severity, including C-reactive protein, Disease Activity Score 28, pain Visual Analog Scale and modified Health Assessment Questionnaire. A nested case–control study from the MDCS found a decreased risk among men and women with moderate (3.67–15.21 g/day) versus low consumption (0.05–3.66 g/day) of alcohol (OR: 0.48; 95% CI: 0.22–1.05), but not among those with high consumption (15.22–194.00 g/day).[24] A study from the SMC showed a nonlinear dose-response relationship between glasses of alcohol per week and risk of RA (RR for >four vs <one glasses/week or never: 0.63; 95% CI: 0.42–0.96).[26] Specific types of alcohol (beer, wine and liquor) were also inversely associated with RA, although the estimates were not statistically significant. The authors also performed an analysis of long-term alcohol consumption, showing that consistent consumption of more than three glasses per week over a period of more than 10 years halved the risk of RA compared with never drinkers (RR : 0.48; 95% CI: 0.24–0.98).
The accumulated evidence on the association between alcohol consumption and RA risk has been quantitatively summarized in two recent meta-analyses and clearly indicates a protective role of moderate consumption of alcohol (<15 g/day) in the development of RA.[73,74]

Methodological Considerations

In general, the accumulated evidence regarding the associations between dietary factors and risk of RA is limited and results are not consistent. This may, in part, be related to the different methodologies that researchers have used in analyzing such a complex exposure as diet.
First of all, the results could be influenced by the choice of study design. Case–control studies may be affected by recall bias, a systematic error due to a different recall of the exposure status between cases and controls. Receiving a diagnosis of RA may cause a more accurate recall and better reporting of dietary habits compared with healthy controls who are not as focused on their health. Therefore it is difficult to draw conclusions based on findings from case–control studies that could either be an overestimate or underestimate of the true risk owing to this type of bias. The prospective cohort design is preferred as it is not affected by recall bias, since the collection of dietary information occurs when all members of the cohort are not affected by the disease. Moreover, cases included in a case–control design may have already changed their diet at the time of the interview owing to the developing of RA, leading to biased estimates of the risk. However, prospective, as well as retrospective, studies can be affected by nondifferential misclassification of the exposure. In fact, people tend to report their food consumption according to what they think is socially acceptable. For example, women tend to report a lower alcohol consumption since high alcohol consumption is considered an unhealthy behavior, while they tend to report higher intake of fruits and vegetables that are considered healthy.[75] Such type of misclassification usually leads to biased estimates.
All studies included in this review used a food frequency questionnaire, with the exception of the studies conducted by Pattison et al. who used a 7-day food diary.[11,13,31] The food diary is a more precise way to collect information regarding daily diet, but the time period of only 1 week does not allow an assessment of long-term diet and seasonal changes. Moreover, to take into account changes in diet over time and better assess the influence of food consumption on the risk of a disease it is important to collect dietary information at different points in time. Of the studies presented in this review, only the SMC[10,26] and the NHS and NHS II collected information at two or more occasions using a food frequency questionnaire.[27,32]
Incident cases of RA were identified in multiple ways by the studies. Case–control studies identified cases from the rheumatology or internal medicine departments of hospitals, while prospective cohort studies identified cases in two different ways: some studies linked the cohort to national registers,[8,10,11,13,26,31] while other studies validated self-reported RA cases by collecting medical records.[9,12,14,18,25,27,28,32,33] The use of self-reported and subsequently validated RA avoids the inclusion of misclassified RA cases; however, true RA cases that have not self-reported their status are missed and included in the study as noncases.
The studies conducted in the EPIC-Norfolk cohort analyzed inflammatory polyarthritis cases, of which only 40% satisfied the ACR criteria for RA definition.[11,13,31] The authors argued that they decided to use inflammatory polyarthritis and not RA definition because the RA criteria did not perform well in the setting of early disease.[76] They conducted analysis stratified by RA status, which did not reveal any difference from the results reported for inflammatory polyarthritis.[11]
Finally, some studies could have been affected by problems related to a low statistical power. One nested case–control study included as few as 14 cases,[29] while the EPIC-Norfolk study identified only 73,[13] and later 88 cases of inflammatory polyarthritis.[11,31] Among prospective cohort studies, the DCH cohort identified only 69 RA cases in a cohort of 57,053 men and women during an average follow-up of 5.3 years.[8] The cohort with the largest number of cases was the NHS with 546 cases identified among 82,063 women ( & ).[9]

Table 1.  Summary of studies reporting measures of association between food consumptions and rheumatoid arthritis.

Study name or location Publication year Design Number of cases vs controls/cohort size Direction of association Rheumatoid arthritis subtypes Ref.
Fish
Greece 1991 Hospital-based case–control 168/137 No association [4]
Greece 1999 Hospital-based case–control 145/188 No association [5]
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
EIRA 2009 Population-based case–control 1889/2145 Inverse ACPA positive: inverse
ACPA negative: no association
RF positive: inverse
RF negative: no association
[7]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
SMC 2013 Prospective cohort 205/32,232 Inverse [10]
Meat
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Dairy products
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
IWHS 2004 Prospective cohort 152/29,368 Inverse [12]
Fruit
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Vegetables
Greece 1999 Hospital-based case–control 145/188 Inverse [5]
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Olive oil
Greece 1991 Hospital-based case–control 168/137 Inverse [4]
Greece 1999 Hospital-based case–control 145/188 Inverse [5]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Coffee
Denmark 2006 Population-based case–control 515/769 Positive Anti-CCP positive: positive
Anti-CCP negative: no association
[15]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
Finland 2000 Prospective cohort 126/18,981 Positive [16]
BWHS 2001 Prospective cohort 71/64,000 Positive only for decaffeinated coffee [17]
IWHS 2002 Prospective cohort 158/31,336 Positive only for decaffeinated coffee RF positive: positive
RF negative: no association
[18]
NHS 2003 Prospective cohort 480/83,124 No association RF positive: positive [19]
DCH 2005 Prospective cohort 69/57,053 No association [8]
Tea
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
BWHS 2001 Prospective cohort 71/64,000 Positive [17]
IWHS 2002 Prospective cohort 158/31,336 Inverse RF positive: inverse
RF negative: no association
[18]
NHS 2003 Prospective cohort 480/83,124 No association RF positive: no association [19]
Alcohol
Leiden, The Netherlands 1990 Hospital-based case–control 135/378 Inverse [20]
King County, WA, USA 1994 Population-based case–control 349/1457 No association [21]
Denmark 2006 Population-based case–control 515/769 No association Anti-CCP positive: inverse
Anti-CCP negative: no association
[15]
EIRA 2009 Population-based case–control 1204/871 Inverse ACPA positive: inverse
ACPA negative: inverse
[22]
CACORA 2009 Population-based case–control 444/533 Inverse ACPA positive: inverse
ACPA negative: no association
[22]
Sheffield, UK 2010 Population-based case–control 873/1004 Inverse Anti-CCP positive: inverse
Anti-CCP negative: inverse
[23]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
Malmö Diet and Cancer Study 2013 Nested case–control 172/688 Inverse RF positive: inverse
RF negative: no association
[24]
Finland 2000 Prospective cohort 126/18,981 No association [16]
IWHS 2002 Prospective cohort 158/31,336 No association [25]
SMC 2012 Prospective cohort 197/34,141 Inverse [26]

RF: Rheumatoid factor.

Table 2.  Summary of studies reporting measures of association between nutrients intake and rheumatoid arthritis.

Study name or location Publication year Design Number of cases vs controls/cohort size Direction of association Comments Ref.
Long-chain n-3 polyunsaturated fatty acids
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
DCH 2005 Prospective cohort 69/57,053 No association [8]
SMC 2013 Prospective cohort 205/32,232 Inverse [10]
Vitamin D
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
IWHS 2004 Prospective cohort 152/29,368 Inverse [12]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2008 Prospective cohort 722/186,389 No association [27]
NHS and NHS II 2012 Prospective cohort 800/119,173 No association Intake during adolescence [28]
Iron
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 88/176 No association [11]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Calcium
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
IWHS 2004 Prospective cohort 152/29,368 No association [12]
Selenium
Finland 1994 Nested case–control 14/28 Inverse [29]
Finland 2000 Nested case–control 122/357 Inverse RF positive: no association
RF negative: inverse
[30]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
Protein
Washington, DC, USA 1996 Population-based case–control 324/1245 Inverse RF positive: inverse
RF negative: no association
[6]
EPIC-Norfolk 2004 Nested case–control 88/176 Positive [11]
NHS 2007 Prospective cohort 546/82,063 No association [9]
Vitamin C
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
EPIC-Norfolk 2004 Nested case–control 73/146 Inverse [13]
EPIC-Norfolk 2005 Nested case–control 88/176 Inverse [31]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS and NHS II 2010 Prospective cohort 787/18,4643 No association [32]
α-tocopherol (vitamin E)
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
Finland 1994 Nested case–control 14/28 Inverse [29]
Finland 2000 Nested case–control 122/357 Inverse RF positive: no association
RF negative: no association
[30]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
DCH 2005 Prospective cohort 69/57,053 No association [8]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
The Women’s Health Study 2008 Randomized, double-blind, placebo-controlled trial 106/39,144 No association Seropositive RA: no association
Seronegative RA: no association
[33]
Carotenoids (α-carotene)
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (β-carotene)
Finland 1994 Nested case–control 14/28 Inverse [29]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
DCH 2005 Prospective cohort 69/57,053 No association [8]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (β-crypthoxantin)
EPIC-Norfolk 2005 Nested case–control 88/176 Inverse [31]
IWHS 2003 Prospective cohort 152/29,368 Inverse [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (lycopene)
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (lutein/zeaxanthin)
EPIC-Norfolk 2005 Nested case–control 88/176 No association [31]
IWHS 2003 Prospective cohort 152/29,368 No association [14]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
Carotenoids (retinol; vitamin A)
Washington, DC, USA 1996 Population-based case–control 324/1245 No association [6]
Finland 1994 Nested case–control 14/28 No association [29]
EPIC-Norfolk 2004 Nested case–control 73/146 No association [13]
NHS and NHS II 2010 Prospective cohort 787/184,643 No association [32]
DCH 2005 Prospective cohort 69/57 053 No association [8]

RA: Rheumatoid arthritis; RF: Rheumatoid factor.

Studies on subtypes of RA, such as RF positive or negative and ACPA positive or negative, are also very limited. Only six studies stratified accordingly to subtypes of RA and found different results between positive and negative RA cases.[6,7,15,18,23,24] The reasons for this could be either the small number of RA cases identified may prevent further stratifications or problems in retrieving information regarding the subtype’s classification for each case.

Conclusion

Studies on diet and risk of RA are limited and often have reported mixed results. It is, therefore, difficult to draw any firm conclusions on the association between different foods and nutrients and RA development and its subtypes (RF positive and negative, ACPA positive and negative). The accumulated evidence is most consistent regarding moderate alcohol consumption and decreased risk of RA. Emerging evidence may also indicate a potentially beneficial role of fish consumption in RA prevention.

Future Perspective

Further well-designed prospective studies are needed to better understand the role of diet in the development of RA. Prospective cohort studies with repeated measurements of diet over time to assess not only short-term, but especially long-term, diet in relation to RA development should be preferred. In addition, since some previous studies have reported a different association with RA depending on method of preparation of foods (e.g., cooked/broiled fish, raw vs cooked vegetables), further studies are needed to analyze also how different methods of cooking influence the observed associations of foods on RA development. Moreover, more attention should be given to the association of diet with specific types of RA.
Single prospective studies may have low statistical power to perform subgroup analyses, for example, by a specific type of RA, or by presence of specific genetic factors. Therefore, analyses of pooled data from available prospective studies should be strongly encouraged. This could also allow the analysis of the interplay of dietary factors with genetic factors in a prospective setting.

Sidebar

Executive Summary

Background

  • Rheumatoid arthritis (RA), an inflammatory autoimmune chronic disease that affects the joints, affects approximately 1% of the adult population.
  • Only smoking has been identified as risk factor for RA, while other modifiable factors, such as diet, are less studied and published results are mixed.

Foods of animal origin

  • Studies on the association between fish, meat and dairy products and RA are limited and results are mixed.
  • There is some evidence that fish consumption and long-chain n-3 polyunsaturated fatty acids are inversely associated with RA risk.

Foods of plant origin

  • Among the limited studies on fruits and vegetables, as well as olive oil, some studies, but not all, observed decreased risk of RA.
  • Beverages
    • Moderate alcohol intake is inversely associated with RA.
    • Caffeinated coffee and tea appear not to be associated with RA risk.
    • Decaffeinated coffee has been linked to an increased risk of RA.

Methodological consideration

  • The methodologies used in the different studies, such as different study designs, varying definition of the outcome and collection of self-reported exposure data, could have led to the differences in the reported results.

Conclusion

  • Studies on diet and RA are limited and results are mixed.
  • The accumulated evidence is most consistent regarding moderate alcohol consumption and decreased RA risk.
  • Emerging evidence is also indicates a potentially beneficial role of fish consumption in prevention of RA.
  • Further studies, preferably with prospective design, are necessary to better understand the role of diet in the development of RA.

References

  1. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun. Rev. 4(3), 130–136 (2005).
  2. Mcinnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365(23), 2205–2219 (2011).
  3. Hagen KB, Byfuglien MG, Falzon L, Olsen SU, Smedslund G. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst. Rev. 1, CD006400 (2009).
  4. Linos A, Kaklamanis E, Kontomerkos A et al. The effect of olive oil and fish consumption on rheumatoid arthritis – a case control study. Scand. J. Rheumatol. 20(6), 419–426 (1991).
  5. Linos A, Kaklamani VG, Kaklamani E et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am. J. Clin. Nutr. 70(6), 1077–1082 (1999).
  6. Shapiro JA, Koepsell TD, Voigt LF, Dugowson CE, Kestin M, Nelson JL. Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption. Epidemiology 7(3), 256–263 (1996).
  7. Rosell M, Wesley AM, Rydin K, Klareskog L, Alfredsson L. Dietary fish and fish oil and the risk of rheumatoid arthritis. Epidemiology 20(6), 896–901 (2009).
  8. Pedersen M, Stripp C, Klarlund M, Olsen SF, Tjonneland AM, Frisch M. Diet and risk of rheumatoid arthritis in a prospective cohort. J. Rheumatol. 32(7), 1249–1252 (2005).
  9. Benito-Garcia E, Feskanich D, Hu FB, Mandl LA, Karlson EW. Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study. Arthritis Res. Ther. 9(1), R16 (2007).
  10. Di Giuseppe D, Wallin A, Bottai M, Askling J, Wolk A. Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2013-203338 (2013) (Epub ahead of print).
  11. Pattison DJ, Symmons DP, Lunt M et al. Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption. Arthritis Rheum. 50(12), 3804–3812 (2004).
  12. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum. 50(1), 72–77 (2004).
  13. Pattison DJ, Silman AJ, Goodson NJ et al. Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case–control study. Ann. Rheum. Dis. 63(7), 843–847 (2004).
  14. Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women. Am. J. Epidemiol. 157(4), 345–354 (2003).
  15. Pedersen M, Jacobsen S, Klarlund M et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res. Ther. 8(4), R133 (2006).
  16. Heliovaara M, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann. Rheum. Dis. 59(8), 631–635 (2000).
  17. Formica Mk PJ, Rosenberg L, Mcalindon Te. Lifestyle factors associated with the development of rheumatoid arthritis (RA): results for the Black Women’s Health Study (BWHS). Arthritis Rheum. 44(Suppl. 9), S376 (2001).
  18. Mikuls TR, Cerhan JR, Criswell LA et al. Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum. 46(1), 83–91 (2002).
  19. Karlson EW, Mandl LA, Aweh GN, Grodstein F. Coffee consumption and risk of rheumatoid arthritis. Arthritis Rheum. 48(11), 3055–3060 (2003).
  20. Hazes JM, Dijkmans BA, Vandenbroucke JP, De Vries RR, Cats A. Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption. Ann. Rheum. Dis. 49(12), 980–982 (1990).
  21. Voigt LF, Koepsell TD, Nelson JL, Dugowson CE, Daling JR. Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology 5(5), 525–532 (1994).
  22. Kallberg H, Jacobsen S, Bengtsson C et al. Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case–control studies. Ann. Rheum. Dis. 68(2), 222–227 (2009).
  23. Maxwell JR, Gowers IR, Moore DJ, Wilson AG. Alcohol consumption is inversely associated with risk and severity of rheumatoid arthritis. Rheumatology (Oxford) 49(11), 2140–2146 (2010).
  24. Bergstrom U, Jacobsson LT, Nilsson JA, Wirfalt E, Turesson C. Smoking, low formal level of education, alcohol consumption, and the risk of rheumatoid arthritis. Scand. J. Rheumatol. 42(2), 123–130 (2013).
  25. Cerhan JR, Saag KG, Criswell LA, Merlino LA, Mikuls TR. Blood transfusion, alcohol use, and anthropometric risk factors for rheumatoid arthritis in older women. J. Rheumatol. 29(2), 246–254 (2002).
  26. Di Giuseppe D, Alfredsson L, Bottai M, Askling J, Wolk A. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study. BMJ 345, e4230 (2012).
  27. Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E. Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann. Rheum. Dis. 67(4), 530–535 (2008).
  28. Hiraki LT, Munger KL, Costenbader KH, Karlson EW. Dietary intake of vitamin D during adolescence and risk of adult-onset systemic lupus erythematosus and rheumatoid arthritis. Arthritis Care Res. (Hoboken) 64(12), 1829–1836 (2012).
  29. Heliovaara M, Knekt P, Aho K, Aaran RK, Alfthan G, Aromaa A. Serum antioxidants and risk of rheumatoid arthritis. Ann. Rheum. Dis. 53(1), 51–53 (1994).
  30. Knekt P, Heliovaara M, Aho K, Alfthan G, Marniemi J, Aromaa A. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology 11(4), 402–405 (2000).
  31. Pattison DJ, Symmons DP, Lunt M et al. Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a population-based prospective study. Am. J. Clin. Nutr. 82(2), 451–455 (2005).
  32. Costenbader KH, Kang JH, Karlson EW. Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women. Am. J. Epidemiol. 172(2), 205–216 (2010).
  33. Karlson EW, Shadick NA, Cook NR, Buring JE, Lee IM. Vitamin E in the primary prevention of rheumatoid arthritis: the Women’s Health Study. Arthritis Rheum. 59(11), 1589–1595 (2008).
  34. Jiang G, Li B, Liao X, Zhong C. Poultry and fish intake and risk of esophageal cancer: a meta-analysis of observational studies. Asia Pac. J. Clin. Oncol. doi:10.1111/ajco.12114 (2013) (Epub ahead of print).
  35. Wu S, Feng B, Li K et al. Fish consumption and colorectal cancer risk in humans: a systematic review and meta-analysis. Am. J. Med. 125(6), 551–559.e555 (2012).
  36. Kolahdooz F, Van Der Pols JC, Bain CJ et al. Meat, fish, and ovarian cancer risk: results from 2 Australian case–control studies, a systematic review, and meta-analysis. Am. J. Clin. Nutr. 91(6), 1752–1763 (2010).
  37. Li YH, Zhou CH, Pei HJ et al. Fish consumption and incidence of heart failure: a meta-analysis of prospective cohort studies. Chin. Med. J. (Engl.) 126(5), 942–948 (2013).
  38. Vrablik M, Prusikova M, Snejdrlova M, Zlatohlavek L. Omega-3 fatty acids and cardiovascular disease risk: do we understand the relationship? Physiol. Res. 58(Suppl. 1), S19–S26 (2009).
  39. Cleland LG, Hill CL, James MJ. Diet and arthritis. Baillieres Clin. Rheumatol. 9(4), 771–785 (1995).
  40. Cantorna MT, Hayes CE, Deluca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J. Nutr. 128(1), 68–72 (1998).
  41. Andjelkovic Z, Vojinovic J, Pejnovic N et al. Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients. Clin. Exp. Rheumatol. 17(4), 453–456 (1999).
  42. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal. 16(7), 705–743 (2012).
  43. Lee DH, Steffes M, Jacobs DR. Positive associations of serum concentration of polychlorinated biphenyls or organochlorine pesticides with self-reported arthritis, especially rheumatoid type, in women. Environ. Health Perspect. 115(6), 883–888 (2007).
  44. Kontogianni MD, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C. Relationship between meat intake and the development of acute coronary syndromes: the CARDIO2000 case–control study. Eur. J. Clin. Nutr. 62(2), 171–177 (2008).
  45. Kaluza J, Wolk A, Larsson SC. Red meat consumption and risk of stroke: a meta-analysis of prospective studies. Stroke 43(10), 2556–2560 (2012).
  46. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res. 54(9), 2390–2397 (1994).
  47. Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int. J. Cancer 119(11), 2657–2664 (2006).
  48. Grant WB. The role of meat in the expression of rheumatoid arthritis. Br. J. Nutr. 84(5), 589–595 (2000).
  49. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet 338(8772), 899–902 (1991).
  50. Kjeldsen-Kragh J, Haugen M, Forre O, Laache H, Malt UF. Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients? Br. J. Rheumatol. 33(6), 569–575 (1994).
  51. Nenonen MT, Helve TA, Rauma AL, Hanninen OO. Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Br. J. Rheumatol. 37(3), 274–281 (1998).
  52. Chua AC, Klopcic BR, Ho DS et al. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice. PLoS ONE 8(11), e78850 (2013).
  53. Boeing H, Bechthold A, Bub A et al. Critical review: vegetables and fruit in the prevention of chronic diseases. Eur. J. Nutr. 51(6), 637–663 (2012).
  54. Slavin JL, Lloyd B. Health benefits of fruits and vegetables. Adv. Nutr. 3(4), 506–516 (2012).
  55. Mosby TT, Cosgrove M, Sarkardei S, Platt KL, Kaina B. Nutrition in adult and childhood cancer: role of carcinogens and anti-carcinogens. Anticancer Res. 32(10), 4171–4192 (2012).
  56. Rees K, Dyakova M, Ward K, Thorogood M, Brunner E. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst. Rev. 3, CD002128 (2013).
  57. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 100(21), 2124–2126 (1999).
  58. Mccord JM. Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. Science 185(4150), 529–531 (1974).
  59. Merry P, Winyard PG, Morris CJ, Grootveld M, Blake DR. Oxygen free radicals, inflammation, and synovitis: and synovitis: the current status. Ann. Rheum. Dis. 48(10), 864–870 (1989).
  60. Comstock GW, Burke AE, Hoffman SC et al. Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann. Rheum. Dis. 56(5), 323–325 (1997).
  61. Lefevre M, Jonnalagadda S. Effect of whole grains on markers of subclinical inflammation. Nutr. Rev. 70(7), 387–396 (2012).
  62. Bouchenak M, Lamri-Senhadji M. Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review. J. Med. Food 16(3), 185–198 (2013).
  63. Bermudez B, Lopez S, Ortega A et al. Oleic acid in olive oil: from a metabolic framework toward a clinical perspective. Curr. Pharm. Des. 17(8), 831–843 (2011).
  64. Alarcon De La Lastra C, Barranco MD, Motilva V, Herrerias JM. Mediterranean diet and health: biological importance of olive oil. Curr. Pharm. Des. 7(10), 933–950 (2001).
  65. Sales-Campos H, Souza PR, Peghini BC, Da Silva JS, Cardoso CR. An overview of the modulatory effects of oleic acid in health and disease. Mini Rev. Med. Chem. 13(2), 201–210 (2013).
  66. James MJ, Gibson RA, Neumann MA, Cleland LG. Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene ref-4 synthesis in rats: a novel approach to inhibition of eicosanoid synthesis. J. Exp. Med. 178(6), 2261–2265 (1993).
  67. Pedersen M, Jacobsen S, Garred P et al. Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis: a nationwide case–control study in Denmark. Arthritis Rheum. 56(5), 1446–1453 (2007).
  68. Garabrant DH, Dumas C. Epidemiology of organic solvents and connective tissue disease. Arthritis Res. 2(1), 5–15 (2000).
  69. Yang CS, Wang ZY. Tea and cancer. J. Natl Cancer Inst. 85(13), 1038–1049 (1993).
  70. Mandrekar P, Catalano D, White B, Szabo G. Moderate alcohol intake in humans attenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Alcohol Clin. Exp. Res. 30(1), 135–139 (2006).
  71. Lu B, Solomon DH, Costenbader KH, Keenan BT, Chibnik LB, Karlson EW. Alcohol consumption and markers of inflammation in women with preclinical rheumatoid arthritis. Arthritis Rheum. 62(12), 3554–3559 (2010).
  72. Waldschmidt TJ, Cook RT, Kovacs EJ. Alcohol and inflammation and immune responses: summary of the 2005 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 38(2), 121–125 (2006).
  73. Jin Z, Xiang C, Cai Q, Wei X, He J. Alcohol consumption as a preventive factor for developing rheumatoid arthritis: a dose-response meta-analysis of prospective studies. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2013-203323 (2013) (Epub ahead of print).
  74. Scott IC, Tan R, Stahl D, Steer S, Lewis CM, Cope AP. The protective effect of alcohol on developing rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 52(5), 856–867 (2013).
  75. Macdiarmid J, Blundell J. Assessing dietary intake: who, what and why of under-reporting. Nutr. Res. Rev. 11(2), 231–253 (1998).
  76. Symmons DP, Hazes JM, Silman AJ. Cases of early inflammatory polyarthritis should not be classified as having rheumatoid arthritis. J. Rheumatol. 30(5), 902–904 (2003).

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