Lower Antioxidant Intake Linked to Endometriosis-Related Rheumatoid Arthritis Risk in Women of Childbearing Age

An association between a lower Composite Dietary Antioxidant Index (CDAI) score and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) was observed among women of childbearing age in a recent study published in the International Journal of Women’s Health,¹ indicating the importance of daily antioxidant intake.

The researchers explained that epidemiological evidence indicates an elevated risk of developing RA in female patients with EM, a disease where tissue like the lining of the uterus grows outside the uterus; this is possibly due to inflammation and oxidative stress. Also, RA predominately affects those aged 20 to 50, with female patients being more susceptible. Therefore, they noted that discovering the factors associated with EM-related RA in female patients is “very important” for future RA management.

Based on this, they noted that antioxidants, like magnesium and vitamins A, C, and E, safeguard the body against oxidative damage and potentially play a protective role against RA development. One past study found that a higher magnesium intake may be inversely associated with RA risk among US adults.² Another found that vitamin E supplementation can improve RA symptoms and patients’ quality of life.³ However, the researchers explained that it is more “clinically relevant” to study the intake of multiple dietary antioxidants as dietary nutrients tend to be simultaneously present.¹

Consequently, the researchers evaluated multiple dietary antioxidants using the CDAI, which reflects each patient’s overall antioxidant exposure. They noted that limited research has been conducted on the association between CDAI score and EM-related RA risk in women of childbearing age. Because of this, the researchers aimed to investigate the relationship between EM, CDAI score, and RA risk in women of childbearing age.

Female patient with arthritis | Image Credit: Evrymmnt - stock.adobe.com

To do so, they used the National Health and Nutrition Examination Survey (NHANES) database, which contains data from 1999 to 2006. Conducted by the National Center for Health Statistics, NHANES is “an ongoing, independent, nationally representative cross-sectional survey of non-institutionalized US civilian populations.”

Those eligible for the study population were women between the ages of 20 and 44 with EM assessments, RA assessments, and complete dietary intake information; the researchers diagnosed EM and RA through a questionnaire. From the database, the researchers extracted the baseline characteristics, comorbidities, family history, treatments, and dietary intake of eligible patients.

The researchers obtained each patient's CDAI score by summing the standardized Z-values of their dietary intakes. Based on these scores, they categorized the patients into 2 groups; those with CDAI calculations lower than the median score (−0.65), who they considered to have lower-level antioxidant intakes, and those with a CDAI score equal to or greater than the median score, who they considered to have a higher-level antioxidant intake. Lastly, they evaluated the additive interaction by using the relative excess risk due to interaction (RERI), the synergy index (S), and the attributable proportion due to interaction (AP).

The study population consisted of 3803 patients, the mean (SD) age being 31.68 (0.17) years. White patients made up most of the population (65.75%), followed by Black patients (12.36%) and those of other racial groups (21.89%).

Of the study population, 74 patients were diagnosed with RA (1.99%). Based on this, the researchers determined the association between a lower CDAI score (OR, 1.85; 95% CI, 1.12-3.04; P = .015) and EM presence (OR, 3.05; 95% CI, 1.19-7.81; P = .023) with RA risk.

Additionally, they found an additive interaction of a lower CDAI score and EM presence on RA risk (OR, 6.19; 95% CI, 2.33-16.43; P < .001; P of trend = .007); there was no significant additive interaction after being assessed by the AP, RERI, and S. However, the researchers observed a joint effect of a lower CDAI score and EM presence on RA risk (OR, 3.94; 95% CI, 1.35-11.51; P = .013).

“The direct connection between EM, low CDAI scores, and an increased risk of RA has not been explicitly confirmed in the literature,” the authors wrote. “However, based on current research it can be hypothesized that the relationship between EM, low CDAI scores, and increased RA risk may be attributable to the individual relationships of EM and low CDAI scores with the risk of RA.”

The researchers acknowledged their limitations, one being that they only observed the relationship between CDAI scores and RA risk, meaning they could not determine causality. Also, although the subjects' lifestyles may change, database limitations prevent the researchers from assessing how these changes impact the outcomes. Due to these limitations, they determined that there was more to explore regarding the associations of EM and CDAI scores with RA risk.

“Future well-designed prospective studies are still needed to validate our results,” the authors concluded.

References

1. Hu H, Wang X, Ren Y, Zhang T, Sun L. Association between composite dietary antioxidant index and the risk of endometriosis-related rheumatoid arthritis in women of childbearing age: a cross-sectional study based on the national health and nutrition examination survey database. Int J Womens Health. 2024;16:717-726. doi:10.2147/IJWH.S453602

2. Fang J, Cao T, Liu C, et al. Association between magnesium, copper, and potassium intakes with risk of rheumatoid arthritis: a cross-sectional study from National Health and Nutrition Examination Survey (NHANES). BMC Public Health. 2023;23(1):2085. doi:10.1186/s12889-023-16906-y

3. Kou H, Qing Z, Guo H, Zhang R, Ma J. Effect of vitamin E supplementation in rheumatoid arthritis: a systematic review and meta-analysis. EurJ Clin Nutr. 2023;77(2):166–172. doi:10.1038/s41430-022-01148-9