Suming Dai ¹ Ping Wang ¹ Sijia Wang ² Hong Chen ¹ Zhixin Cui ¹ Wenhai Lu ³ Ziyi Zhou ⁴ Nan Zhang ⁵ Zhuo Wang ⁶ Tengfei Lin ⁶ Yun Song ⁶ Lishun Liu ⁴ Xiao Huang ⁷ Ping Chen ⁸ Genfu Tang ⁹ Yong Duan ¹⁰ Hao Zhang ⁶ Binyan Wang ¹¹ Yan Yang ¹ Zezhong Tian ^1*

• ¹ Sun Yat-sen University, Guangzhou, China
• ² Shenzhen Luohu District Chronic Disease Prevention and Treatment Hospital, Shenzhen, China
• ³ Pingdi Public Health Service Center, Shenzhen, China
• ⁴ Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
• ⁵ Department of Cardiology, First Hospital, Peking University, Beijing, Beijing Municipality, China
• ⁶ College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, Beijing Municipality, China
• ⁷ Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
• ⁸ College of Pharmacy, Jinan University, Guangzhou, China
• ⁹ School of Heath Administration, Anhui Medical University, Anhui, China
• ¹⁰ Yunnan Key Laboratory of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
• ¹¹ Institute of Biomedicine, Anhui Medical University, Hefei, China

Background: Existing epidemiological studies investigated the association between single vitamin and hypertension. However, the potential relationship between the level of circulating multivitamins and blood pressure have not been explored. We aimed to investigate the association between multiple fat-soluble vitamin levels and blood pressure. Methods: 2052 participants with essential hypertension were sampled nationwide. The plasma concentrations of fat-soluble vitamins (A, E, D, K) were assessed using liquid chromatography coupled with mass spectrometry method. Participants were categorized into different co-exposure patterns using unsupervised K-means clustering method. The multiple linear regression model was employed for subsequent analyses. Results: Participants were classified into two co-exposure patterns of fat-soluble vitamins. The levels of vitamins were relatively low in pattern 1, compared to pattern 2.Participants in pattern 2 had no significantly different blood pressure levels compared to pattern 1. However, the plasma 25-hydroxyvitamin D3 (VD3) levels were negatively associated with SBP (logarithmic 10 transformed) (β = -0.002, 95% CI: -0.004,0); participants in the fourth α-tocopherol quartile had mean SBP levels that were 1.02% (95% CI: 0.43%, 1.61%) greater than those in the lowest quartile (p for trend < 0.01).Besides, no significant relationships were found between plasma VA/VK concentrations and blood pressure. Discussion: Although no significant association between fat-soluble vitamin 5 co-exposure patterns and blood pressure was found, further analyses could imply that plasma α-tocopherol levels may offset the potential protective effect of plasma VD3 on blood pressure among hypertensive adults. This provided a novel perspective for exploring the joint effects of fat-soluble vitamins on blood pressure. Further studies are warranted to better understand the implications.