<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> Piper Biosciences. <h3>Background/Synopsis</h3> The effectiveness of a plant sterol gummy supplement was studied in a South-Asian (SA) patient population with low to moderate cardiovascular disease (CVD) risk as defined by an Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score of < 7.5%, and a low density lipoprotein (LDL)-C level of 120-189 mg/dl. Statin therapy is often not recommended to patients with ASCVD score < 7.5% even in the presence of risk accelerators such as SA ethnicity, to which the 2018 National Lipid Association (NLA) guidelines call attention. <h3>Objective/Purpose</h3> Phytosterols are known to lower LDL-C and are included in NLA and other global guidelines. This study aimed to establish their impact on LDL-C levels in 'borderline' risk SAs. <h3>Methods</h3> 50 SAs were recruited during the COVID 19 pandemic, mainly from a preventive cardiology clinic dedicated to reducing SA heart disease risk. Eligible subjects had a 10-year CV risk score (ASCVD) <7.5% and LDL-C level of 120-193mg/dl at study enrollment. Subjects intolerant of or refusing statins were also recruited. The study was administered with a fully decentralized design, leveraging mailed supplements, televisits, remote lab collection, and SMS-based communications. Upon completing baseline labs and surveys, subjects were provided a 90-day supply of 1400mg phytosterol gummy supplements in individual packets (Piper Biosciences, Los Altos, CA) to be ingested twice daily. Subjects were instructed to continue current lifestyle habits and report major dietary pattern deviations. The primary endpoint was LDL-C reduction at 3 months. Pre- and post-study surveys were administered to assess diet and lifestyle. <h3>Results</h3> 33 of the 50 subjects successfully completed the protocol. A significant overall reduction in LDL-C of 5.8% was observed (p=0.03) (Table 1, Figure 1). Subgroup A (n=27) completed the protocol with no significant dietary variation, demonstrating a significant LDL-C reduction of 6.5% (p=0.002), as well as a total cholesterol (TC) reduction of 4.4% (p=0.01). There was no significant change in other metrics, including BMI, fasting glucose, or HbA1C. Patients who completed the protocol but reported worsening dietary habits (Subgroup B, n=6) showed an average increase in LDL-C of 6% (p=0.2) and in TC of 8% (p=0.002). Survey responses indicate that 94% of subjects would be interested in long-term supplementation if recommended by physician and 80% would prefer taking it proactively to manage cholesterol levels. <h3>Conclusions</h3> Plant sterols are an effective and sustainable means to lower LDL-C in middle-aged SAs, whose CV risk is often underestimated. To our knowledge this study represents the first demonstration of phytosterol effectiveness in the highest coronary disease risk population globally.