Folic Acid Supplementation Increases Cardiac Parasympathetic Modulation of Heart Rate in Habitually Endurance Trained and Untrained Middle‐Aged Men
Authors: Donnell Emma O' , Craig Jennifer , Akam Elizabeth C. , Bailey Stephen J. 
Published: April 2020

IntroductionAgeing is associated with decreased, and exercise training increased, parasympathetic modulation of heart rate (HR). Cardiac parasympathetic control has prognostic significance in cardiac disease, but the mechanisms remain unclear. Nitric oxide (NO) is thought to play an important role, both at the level of the sinoatrial node and through modulation of autonomic control of HR. Folic acid (FA) increases vascular NO levels. The modulatory effects of FA, ageing and exercise training on autonomic control of HR, are unknown. Thus, we tested the hypothesis that FA supplementation would increase cardiac parasympathetic modulation of HR in habitually trained and untrained middle‐aged men, with FA and exercise training eliciting greater increases than either exercise or FA alone.MethodsTwo groups of healthy, normotensive, age‐matched (55±3 years; overall mean±SEM), habitually endurance trained (n=14; VO2peak 49±1 ml/kg/min; MAtr;) and untrained (n=14; 37±1 ml/kg/min; MAun) men were studied. A comparator group of young (26±1 years) untrained (n=14; 50±1 ml/kg/min; YMun) men were also studied. Heart rate variability (HRV), an index of cardiac modulation of HR, was recorded during 7 minutes of supine rest using lead II of an ECG, both before and after 4 weeks of FA supplementation (5mg/day). Fast Fourier frequency domain measures were determined: high frequency (HF), low frequency (LF), and very LF (VLF). Due to skewness, HF, LF and VLF data were log transformed. LF:HF ratio and total (VLF+LF+HF) HRV were calculated. Circulating levels of folate, plasma nitrite, a stable metabolite of NO, were determined.ResultsAt baseline, HFlog, LFlog and Total HRV did not differ (p>0.05) between MA groups, but were higher in YMun (p<0.05). VLFlog, LF:HF, and folate levels did not differ (p>0.05) between groups. Resting HR was lower (p<0.05) in MAtr versus MAun, but did not differ (p>0.05) between MAun and YMun. Nitrite levels were highest (p<0.05) in MAtr.Post‐FAWithin‐groups, HFlog, LFlog, Total HRV and folate levels were increased (p<0.05). LF:HF, VLFlog, HR and nitrite levels were unaltered (p<0.05). Between‐groups, HFlog, LFlog, and Total HRV remained similar (0>0.05) between MA groups, and higher (p<0.05) in YMun. VLFlog, LF:HF, and folate levels did not differ (p>0.05) between groups. Resting HR remained lower (p<0.05) in MAtr versus MAun, and similar (p>0.05) between MAun and YMun. Nitrite levels were higher (p<0.05) in MAtr versus YMun.ConclusionWe report similar HF, LF and Total HRV, and lower resting HR, in trained versus untrained MA men. After four‐weeks of FA supplementation, HF, LF and Total HRV were increased, and HR unaltered, in both groups. These findings suggest cardiac parasympathetic control of HR does not differ between endurance trained and untrained MA men. In contrast, short‐term FA supplementation augments cardiac parasympathetic modulation in both groups. Further, exercise training and FA do not confer additive effects. Given the clinical significance of cardiac parasympathetic modulation of HR, FA may independently provide protective cardiac autonomic effects with healthy ageing in men.Support or Funding InformationThe research was supported by the National Institute for Health Research (NIHR) Leicester BRC.