TYPE Systematic Review PUBLISHED 31 October 2022 DOI 10.3389/fnut.2022.1011002 OPEN ACCESS EDITED BY Ming Yang, Sichuan University, China REVIEWED BY Mahesh Kumar Samota, Central Institute of Post-Harvest Engineering and Technology (ICAR), India Jun Ren, Fudan University, China Maulana Yusuf Alkandahri, Universitas Buana Perjuangan Karawang, Indonesia Evelyn Frias-Toral, Catholic University of Santiago de Guayaquil, Ecuador *CORRESPONDENCE Phiwayinkosi V. Dludla pdludla@mrc.ac.za SPECIALTY SECTION This article was submitted to Clinical Nutrition, a section of the journal Frontiers in Nutrition RECEIVED 03 August 2022 ACCEPTED 29 September 2022 PUBLISHED 31 October 2022 CITATION Dludla PV, Nkambule BB, Nyambuya TM, Ziqubu K, Mabhida SE, Mxinwa V, Mokgalaboni K, Ndevahoma F, Hanser S, Mazibuko-Mbeje SE, Basson AK, Sabbatinelli J and Tiano L (2022) Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials. Front. Nutr. 9:1011002. doi: 10.3389/fnut.2022.1011002 Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials Phiwayinkosi V. Dludla 1,2 *, Bongani B. Nkambule 3 , Tawanda M. Nyambuya 4 , Khanyisani Ziqubu 5 , Sihle E. Mabhida 1 , Vuyolwethu Mxinwa 3 , Kabelo Mokgalaboni 3,6 , Fransina Ndevahoma 4 , Sidney Hanser 7 , Sithandiwe E. Mazibuko-Mbeje 5 , Albertus K. Basson 2 , Jacopo Sabbatinelli 8 and Luca Tiano 9 1 Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa, 2 Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa, 3 School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa, 4 Department of Health Sciences, Namibia University of Science and Technology, Windhoek, Namibia, 5 Department of Biochemistry, North-West University, Mmabatho, South Africa, 6 Department of Life and Consumer Sciences, University of South Africa, Florida Campus, Roodepoort, South Africa, 7 Department of Physiology and Environmental Health, University of Limpopo, Sovenga, South Africa, 8 Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, 9 Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)- related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or Frontiers in Nutrition 01 frontiersin.org