Background/Purpose: Antioxidant components in food may be biologically relevant to the prevention of rheumatoid arthritis (RA). Evidence from prospective cohort studies regarding the relationship between blood levels of food source antioxidants and risk of RA is limited. The aim of present study was to examine the association between circulating carotenoids and RA risk.    

Methods: We conducted a nested case-control study consisting of 228 incident RA cases and 674 matched controls with prospectively measured plasma carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin) levels in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS II).  Incident RA cases were diagnosed >3 months after blood draw, matched on birth year, race, menopausal status/hormone use, time of day and fasting status, with 3 controls. Smoking, alcohol intake, dietary data, body mass index (BMI) and physical activity were from the questionnaire prior to blood draw. Seropositive RA was defined as positive RF or ACPA by chart review or measurement. Logistic regressions models estimated odds ratios (OR) and 95% confidence intervals (CI) for RA risk associated with each circulating carotenoid.

Results: The median follow-up time from blood draw until RA diagnosis was 8.6 years (0.3 to 19 years). In the multivariable models, no significant associations were found between any plasma carotenoids and risk of all RA, or of seropositive RA. In contrast, we found circulating α-carotene, β-carotene, β-cryptoxanthin and total carotenoids were inversely associated with seronegative RA risk.  Women in the highest quartile of α-carotene were associated with a 52% reduction in seronegative RA risk (OR=0.48; 95% CI, 0.25-0.92). The risk reduction of the highest quartile of β -carotene was 51% (OR=0.49; 95% CI: 0.24-1.00). Circulating β-cryptoxanthin was also associated with the reduced risk of seronegative RA (p trend 0.05). Being in the highest quartile of total plasma carotenoid concentration was associated with a 58% reduced seronegative RA risk (OR=0.42, 95% CI: 0.22-0.81, ptrend 0.03). There was no significant inverse association of lycopene with seronegative RA.

Conclusion: Circulating carotenoid metabolites were associated with a reduced risk of seronegative RA, but not seropositive RA, suggesting different mechanisms for development of these two RA phenotypes. Further studies are needed to confirm our finding.

 

Table. The association between circulating   carotenoids (quartiles) and risk of seropositive and seronegative RA (Odds   ratio and 95% confidence interval)*
Seropositive   RA (n=135)
	Q1	Q2	Q3	Q4	P trend
Lutein/zeaxanthin	1.00	1.08(0.62,1.89)	1.32(0.76,2.28)	1.36(0.79,2.37)	0.47
β-cryptoxanthin	1.00	0.87(0.51,1.49)	1.00(0.58,1.72)	1.17(0.67,2.03)	0.93
Lycopene	1.00	1.40(0.81,2.42)	1.53(0.90,2.62)	1.20(0.69,2.10)	0.74
α-carotene	1.00	0.96(0.56,1.67)	1.09(0.63,1.88)	1.28(0.74,2.22)	0.82
β-carotene	1.00	1.50(0.87,2.59)	1.10(0.61,1.98)	1.72(0.98,3.03)	0.44
Total carotenoids**	1.00	1.26(0.72,2.22)	1.67(0.97,2.90)	1.51(0.85,2.69)	0.44
Seronegative   RA (n=93)
Lutein/zeaxanthin	1.00	1.43(0.80,2.57)	0.81(0.42,1.55)	0.64(0.32,1.28)	0.07
β-cryptoxanthin	1.00	0.82(0.46,1.45)	0.52(0.27,0.99)	0.54(0.28,1.05)	0.05
Lycopene	1.00	1.16(0.63,2.12)	0.89(0.47,1.70)	1.01(0.55,1.88)	0.87
α-carotene	1.00	0.50(0.27,0.91)	0.63(0.34,1.14)	0.48(0.25,0.92)	0.07
β-carotene	1.00	0.77(0.42,1.39)	0.87(0.48,1.58)	0.49(0.24,1.00)	0.07
Total carotenoids**	1.00	0.37(0.20,0.71)	0.62(0.35,1.11)	0.42(0.22,0.81)	0.03
* Total carotenoids were the sum of   lutein/zeaxanthin, β-cryptoxanthin, total lycopene, α-carotene and   β-carotene. ** Adjusting for matching factors (age, menopausal status,   postmenopausal hormone use, and day, time, and fasting status at the time of collection),   smoking status (never, past, current) and body   mass index. Additional adjustment for alcohol consumption, healthy eating   index, physical activity and total calories intake did not change the   results.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-carotenoids-and-subsequent-risk-of-rheumatoid-arthritis/