Effects of Short‐term Folic Acid Supplementation on Brachial Artery Endothelial Function in Habitually Trained and Untrained Postmenopausal Women
Authors: Craig Jennifer , Akam Elizabeth C. , Bailey Stephen J. , Cox Nick J. , Ferguson Richard A. , O’Donnell Emma 
Published: April 2020

BackgroundExercise‐mediated increases in blood flow, a known nitric oxide (NO) stimulus, is a key signal in adaptations to exercise training, including augmented endothelial function. However, habitually endurance trained postmenopausal women (PMW) demonstrate similar brachial artery endothelial function as untrained PMW, suggesting the vascular adaptations to exercise training are mitigated. Folic acid (FA), a B‐vitamin, increases endothelium‐derived NO production. We tested the hypothesis that short‐term FA supplementation would augment endothelial function in association with increased circulating NO levels in endurance trained and untrained PMW, but that trained PMW would demonstrate greater vascular improvements.MethodsTwo groups of healthy, normotensive, age‐matched (57±1 years; overall mean±SEM), habitually endurance trained (n=12; VO2peak 40±1 ml/kg/min; PMWtr) and untrained (n=12; VO2peak 29±1 ml/kg/min; PMWun) PMW volunteered for the study (Table
1). Brachial artery endothelial function was assessed using flow‐mediated dilation (FMD) before and after 4‐weeks of FA supplementation (5mg/day). Blood pressure (BP) was assessed using an automated device. Primary outcome measures included: FMD% (percentage change from baseline diameter to peak diameter), shear rate (area under the curve from post‐occlusion cuff release to peak diameter; SRAUC), and FMD% adjusted for SRAUC (FMD/SRAUC). Blood samples were also obtained and analyzed for total serum folate, plasma nitrite, and asymmetric dimethylarginine (ADMA), an inhibitor of flow mediated‐induced NO and vasodilation.ResultsBaselineBetween‐groups, cardiorespiratory fitness was higher (p<0.05) and body mass index lower (p<0.05) in PMWtr (Table
1). Brachial artery measures, BP and blood biomarkers did not differ (p>0.05; Tables
1 and
2).Post‐FAWithin‐groups, serum folate concentration was increased (p<0.05), and plasma ADMA unaltered (p>0.05) in both groups. Plasma nitrite concentration was increased (p<0.05) in PMWtr only. FMD% and SRAUC were increased (p<0.05) in PMWun only. FMD/SRAUC was augmented (p<0.05) in both groups. Between‐groups, SRAUC was higher (p<0.05) in PMWun. Plasma nitrite (p>0.05) and FMD/SRAUC (p>0.05) did not differ between groups.ConclusionsHabitually endurance trained PMW demonstrate similar endothelial function, circulating nitrite, and ADMA concentrations as their untrained counterparts. Four weeks of FA supplementation augmented vascular function, specifically FMD/SRAUC, in both groups, but did not influence ADMA. Nitrite concentration was increased post‐FA in trained PMW only. These findings suggest that in PMW: i) habitual endurance training does not modulate vascular function nor circulating levels of ADMA or nitrite; ii) FA may, in the face of estrogen deficiency, augment vascular responsiveness to shear stress, but that habitual endurance training does not further augment this responsiveness.Support or Funding InformationThe research was funded by Loughborough University and supported by NIHR Leicester Research Centre
Group characteristics

PMWun (n=12)

PMWtr (n=12)

Age (years)

57±1

57±1

Height (cm)

164±1

166±2

Weight (kg)

62±2

59±2

BMI (kg/m2)

23±1

21±1
†

VO2peak (ml/kg/min)

29±1

40±1
†

Heart rate (beats/min)

58±2

55±2

Systolic BP (mmHg)

118±3

113±2

Diastolic BP (mmHg)

76±2

73±2

MAP (mmHg)

90±2

86±2

All values are mean±SEM
BMI, body mass index; VO2peak, peak oxygen uptake; BP, blood pressure; MAP, mean arterial pressure
†Significant between group differences, p<0.05
Brachial artery responses and blood biomarker concentrations pre‐ and post‐folic acid

PMWun (n=12)

PMWtr (n=12)

Pre‐FA

Post‐FA

Pre‐FA

Post‐FA

Dbase (mm)

3.15±0.11

3.12±0.13

3.29±0.08

3.34±0.09

Dpeak (mm)

3.26±0.11

3.26±0.13

3.43±0.09

3.49±0.10

FMD (%)

3.53±0.33

4.65±0.50
*

4.21±0.40

4.53±0.40

SRAUC (a.u)

5969±623

6899±462
†
*

5885±371

5236±228

FMD/SRAUC (a.u)

6.33±0.74

6.80±0.64
*

7.45±0.81

8.81±0.87
*

TTP (secs)

36.8±3.2

40.2±2.5

38.5±3.5

36.4±2.0

Folate (ng/ml)

7.9±0.8

20±0
*

10.5±1.0

20±0
*

Nitrite (nM)

72.9±9.7

65.5±9.1

57.9±7.1

92.3±15.2
*

ADMA (μmol/L)

0.41±0.05

0.42±0.05

0.53±0.08

0.48±0.07

All values are mean±SEM. Dbase, baseline brachial artery diameter; Dpeak, peak brachial artery diameter; FMD, flow mediated dilation; TTP, time to Dpeak; SRAUC shear rate area under the curve from cuff‐release to Dpeak; FMD/SRAUC, FMD normalised to SRAUC; ADMA, asymmetric dimethylarginine
†Between groups, within condition p<0.05
*Within‐groups, pre‐ vs post‐FA, p<0.05