Dietary supplementation with polyphenol-rich Salicornia ramosissima extracts: Assessing safety, efficacy, and impact on cardiovascular health biomarkers in healthy volunteers

• Three-month oral supplementation with S. ramosissima extracts was found safe in healthy volunteers. • .Minor adverse effects, mostly gastrointestinal and urinary, showed no significant difference from placebo. • Biochemical changes with Salicornia treatment included lowered LDL, increased GFR, reduced homocysteine and GGT, and higher potassium. • . S. ramosissima supplementation led to changes in plasma biomarkers related to cardiovascular disease. The importance of diet in preventing non-communicable diseases is well established, with polyphenol consumption suggested to impact cardiovascular disease development. Salicornia ramosissima synthesizes high amounts of phytochemicals under environmental stress. In a randomized controlled clinical trial on 90 healthy volunteers, we evaluated the safety of supplementation with 1 g of polyphenol-rich S. ramosissima extracts from salt marshes and hydroponic sources over three months. No differences in adverse effects were observed between extract-treated and placebo subjects. Salicornia extract from marshes (SM) increased glomerular filtration rate and reduced LDL cholesterol. SM treatment also modulated plasma markers related to cardiovascular disease: MERTK, Gal-9, ADM, TF, PRSS27, HAOX1, IL-18, PAPPA, TNFRSF1A, TIE2 and FGF-21 proteins were downregulated while SRC levels were upregulated. Therefore, under the studied conditions of use, Salicornia extracts consumption is safe and SM induced biochemical and proteomic changes related to cardiovascular health.