Dietary Antioxidant Intake and Associations with Self-Reported Pain Among Adults Living with Sickle Cell Disease in the U.S
Stephaine Wildridge, Li Yang, Shanna Yang, Sara Turner, Samuel M Degenhard, Danetta Hooks, Djaina-Shae Dervil, Samuel Zamora, Rebecca M Metellus, Siobhan M Lawler, Ashley Buscetta, Allison Brichacek, Vence Bonham, Nicole FarmerAbstract
Background
Symptom management of sickle cell disease (SCD) remains the primary treatment modality. Dietary antioxidants have been a focus of research, as oxidative stress is a key pathway in the pathophysiology of SCD. Assessing dietary intake through food of specific antioxidants, such as vitamin E, vitamin C, vitamin A and carotenoids, and flavonoids like quercetin are related to other pathophysiological pathways, such as inflammation, and could prove to be helpful in learning how nutrition and diet intake can assist in managing symptoms. Specifically, the antioxidant quercetin has been found through in vitro studies to prevent sickling of red blood cells. Prior research in adults living with SCD in the United States has involved evaluating antioxidant vitamin supplementation on symptoms. In this analysis, we sought to explore antioxidant exposure from foods and determine if associations with self-reported pain and inflammatory markers are present.
Methods
The Diet and SCD Study is an observational, mixed-methods investigation initiated in 2022 with a target enrollment of 80 adults with sickle cell disease (SCD) residing in the United States. The primary objective is to assess associations between dietary intake and disease severity among non-hospitalized adults (≥18 years) with confirmed SCD and stable (steady-state) symptoms for at least 4 weeks. The study employs a hybrid design incorporating both in-person and telehealth procedures. Data collection includes clinical assessments, electronic patient-reported outcome surveys, and laboratory measurements, including SCD-specific biomarkers. Dietary interviews consisted of two 24-hour dietary recall interviews conducted by nutrition staff. The 24-hour dietary recalls were analyzed using the Nutrition Data System for Research (NDSR), a computer-based software application developed at the University of Minnesota Nutrition Coordinating Center (NCC). Self-reported pain was measured using the ASCQ-Me measures for pain impact (acute), severity and frequency over the prior 12 months. Inflammation was measured using hsCRP.
Results
Among the study participants recruited to date (n = 64), the mean age was 42.7 (+-12.25, 21-71) years, 71.9% were female. Mean energy intake was 1,829 kcal/day. Estimated vitamin A intake, combining retinol and provitamin A carotenoids, was approximately 600–650 µg retinol activity equivalents (RAE) per day, generally sufficient to meet the RDA for women and approaching the RDA for men. Mean vitamin C intake was 87.8 mg/day, exceeding the RDA for women and closely approximating the RDA for men. Selenium intake averaged 104 µg/day, nearly twice the adult RDA. In contrast, vitamin E intake (IU) fell below the 15 mg/day RDA for α-tocopherol. Quercetin intake of 9.3 mg/day was consistent with reports of intake for U.S. adults. Vegetable intake averaged approximately 3 servings per day. All types of antioxidants were significantly directly associated with total vegetable serving intake (p < 0.005). Pain impact scores were directly correlated with CRP levels (r = 0.32, P < 0.001); while the antioxidants Vit E (beta-tocopherol) r=-0.255(p = 0.045), manganese (r=-0.29, p = 0.02) and quercetin (r=-0.28, p = 0.026) were inversely correlated. Of all of the antioxidant nutrients, only quercetin was significantly associated with CRP levels (r=-0.31, p = 0.015). Pain severity and frequency over the prior 12 months were not associated with any of the dietary antioxidants.
Conclusions
Dietary intake of antioxidants from food were associated with pain impact, a self-reported outcome related to more acute pain in a sample of steady-state adults living with SCD in the U.S. Quercetin, an antioxidant with in vitro anti-sickling properties was not only favorably associated with pain, but also inflammation. The findings from this cross-sectional study cannot establish causality but support the need for future research, including dietary intervention studies examining antioxidant nutrients as potential adjunctive approaches for managing pain and inflammation.