α-Tocopherol influences glycaemic control and miR-9-3 DNA methylation in overweight and obese women under an energy-restricted diet: a randomized, double-blind, exploratory, controlled clinical trial

Rafaella Cristhine Pordeus Luna, Mayara Karla dos Santos Nunes, Mussara Gomes Cavalcante Alves Monteiro, Cássia Surama Oliveira da Silva, Rayner Anderson Ferreira do Nascimento, Raquel Patrícia Ataíde Lima, Flávia Cristina Fernandes Pimenta, Naila Francis Paulo de Oliveira, Darlene Camati Persuhn, Aléssio Tony Cavalcanti de Almeida, Alcides da Silva Diniz, Cristina Wide Pissetti, Rodrigo Pinheiro Toledo Vianna, Flavia Emília Leite de Lima Ferreira, Maria da Conceição Rodrigues Gonçalves, Maria José de Carvalho Costa

Excess weight is a strong risk factor for the development of dysglycaemia. It has been suggested that changes in the metabolism microRNAs, small non-coding RNAs that regulate gene expression, could precede late glycaemic changes. Vitamin E in turn may exert important functions in methylation and gene expression processes. This study aimed to determine the effect of α-tocopherol on glycaemic variables and miR-9-1 and miR-9-3 promoter DNA methylation in overweight women. A randomized, double-blind, exploratory, placebo-controlled study was conducted in overweight and obese adult women (n = 44) who ingested synthetic vitamin E (all-rac-α-tocopherol), natural source vitamin E (RRR-rac-α-tocopherol) or placebo capsules and were followed up for a period of 8 weeks. Supplemented groups also received dietary guidance for an energy-restricted diet. An additional group that received no supplementation and did not follow an energy-restricted diet was also followed up. The intervention effect was evaluated by DNA methylation levels (quantitative real-time PCR assay) and anthropometric and biochemical variables (fasting plasma glucose, haemoglobin A1C, insulin, and vitamin E). Increased methylation levels of the miR-9-3 promoter region (P < 0.001) and reduced haemoglobin A1C (P < 0.05) were observed in the natural source vitamin E group after intervention. Increased fasting plasma glucose was observed in the synthetic vitamin E group, despite the significant reduction of anthropometric variables compared to the other groups. α-Tocopherol from natural sources increased methylation levels of the miR-9-3 promoter region and reduced haemoglobin A1C in overweight women following an energy-restricted diet. These results provide novel information about the influence of vitamin E on DNA methylation. ClinicalTrials.gov, NCT02922491. Registered 4 October, 2016.