A survey was conducted through the SECUBA (SEguridad alimentaria en CUba y Buena Alimentación) research program in Cuban healthy smokers living in Guantánamo and in Havana. The aim of the survey was to investigate biological and nutritional factors connected with the occurrence of zero epidemic neuropathy (EN) observed in Guantánamo urban area since the disease emerged in Cuba. Blood riboflavin status and carotenoid and selenium concentrations were higher in Guantánamo than in Havana smokers. Food dietary quantities of plantain banana, pepper (Capsicum spp.), bovine meat and milk products were higher in Guantánamo. Inversely, foods rich in cholesterol, especially eggs, were more consumed in Havana. Through riboflavin, carotenoid and selenium contents and specific antioxidants substances (indoleamines, capsaicin), the foods more consumed in Guantánamo could be considered as EN protective factors. Disease protective effects could be exerted via enhancement of defence mechanisms against free radical damage and related mechanisms focused on redox recycling of glutathione and local protection from carotenoids. Finally, the results of the present study should help Cuba, through a better EN control, to improve long-term food safety and define healthier dietary habits.