Clinical and Computational Exploration of Red Date Fruit Vinegar: Synergistic Effects on Cardiovascular and Type 2 Diabetes Pathways

Zeshan Ali^1*Hamad Rafique^2*Rana Adnan Tahir³Tania Saeed⁴Muhamad Amir Rasheed⁵Ishrat Khan⁶Tawfiq Alsulami⁷Muqadas Shahzadi⁸Mariam Laraib Amir⁹Fangchao Cui¹Jianrong Li^1*

• ¹College of Food Science and Technology, Bohai University, Jinzhou Liaoning, 121013, China, Jinzhou Liaoning, China
• ²School of Food Engineering and Nutrition Science, Shaanxi Normal University, Xi'an, China
• ³Department of Biology, Sultan Qaboos University, Muscat, 123, Oman, Muscat, Oman
• ⁴Department of Biosciences, COMSATS University Islamabad, Sahiwal campus, Sahiwal, Punjab, Pakistan
• ⁵Business School, Division of Management & Administrative Science, University of Education, Lahore, Pakistan, Lahore, Pakistan
• ⁶School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
• ⁷Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
• ⁸Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, Pakistan
• ⁹Department of Bicinformatics and Biotechnology, Government College University Faisalabad, Pakistan, Faisalabad, Punjab, Pakistan, Pakistan

Dates (Phoenix dactylifera), often questioned for their high sugar content, may provide anti-diabetic benefits through their phytochemicals. Date vinegar offers a potentially effective alternative with reduced sugar content and enhanced bioactivity. This study evaluated the effects of date vinegar on glycemic control and lipid profiles in adults with type 2 diabetes mellitus (T2DM) and dyslipidemia while exploring the molecular mechanisms of its bioactive compounds in managing cardiovascular diseases (CVDs) and T2DM. A 10-week randomized controlled trial assessed the clinical effects of date vinegar. Complementary experiments explored therapeutic mechanisms through computational analysis and assessed sugar reduction and bioactive preservation under varying drying conditions. Fifty adults with T2DM and dyslipidemia were randomized into two groups: 25 participants received 20 mL of date vinegar daily, while 25 received a placebo. Clinical parameters were measured, including HbA1c, LDL cholesterol, and fasting blood sugar. Computational docking and molecular dynamics simulations investigated interactions of bioactive compounds with key protein targets. Significant improvements were observed: HbA1c reduced from 6.85% to 6.08%, LDL cholesterol from 121.05 mg/dL to 111.09 mg/dL, and fasting blood sugar from 168.4 mg/dL to 147.6 mg/dL (p < 0.05). Key compounds with stable protein-ligand complexes confirmed were bound to targets such as ACE, β1AR, hATRs, AR, DPP-IV, and SGLT1. Higher drying temperatures reduced sugar content to match fresh dates but compromised bioactive integrity. Date vinegar offers a dual target therapeutic strategy for managing T2DM and CVDs, supported by clinical and computational findings.