Short-term folinic acid supplementation and aerobic exercise improve vascular reactivity in HIV-infected individuals

Abstract

The aim of this study was to determine the effect of supervised exercise and folinic acid supplementation on endothelial function in HIV-infected individuals. A randomized clinical trial, double blinded, was conducted with 16 HIV-infected individuals, antiretroviral therapy (at least 6 months) with undetectable viral load (<50 copies/mL), and CD4 count > 200 cells/mm. The subjects were randomized to aerobic exercise (n = 5) and daily intake for 4 weeks of 5 mg of folinic acid (n = 6) or placebo (n = 5) groups. To assess endothelial function, venous occlusion plethysmography in the brachial artery by the protocol of reactive hyperemia was performed. The aerobic protocol consisted in cycling exercise, 3 times/week at 60-80% VOmax, for 4 weeks. Exercise group (Δ6.5 mL/min/100 mL) and folinic acid group (Δ7.3 mL/min/100 mL) improved reactive hyperemia, but no difference was found in placebo group (from Δ -0.3 ml/min/100 ml, time p < 0.001, interaction p = 0.02). Results demonstrate that supervised exercise and folinic acid supplementation in very short term improve endothelial function in HIV-infected individuals. As exercise and folate supplementation are safe and relatively inexpensive, this finding deserves more attention in large randomized clinical trials in an attempt to reduce cardiovascular risk in HIV-infected population.

Increased vascular function and superoxide dismutase activity in physically active vs inactive adults living with HIV

“…Actually, when it comes to HIV-infected patients, little evidence on the effects of exercise on vascular function exists-we could only find a single cross-sectional study showing that arterial compliance was greater in fit vs unfit HIV-infected individuals 40 and a recent randomized clinical trial, with a small sample size, indicating that short-term aerobic exercise and folinic acid supplementation improve vascular reactivity in this population. 41 Therefore, we have extended the current knowledge by originally demonstrating that not only macrovascular function, but also angiogenesis and, to a certain extent, antioxidant activity might be favored in patients that underwent regular physical training. This is particularly important considering the high prevalence of endothelial dysfunction and cardiovascular diseases among this group.…”

“…Although our results of vascular function seem to be aligned to prior research in other cohorts, we cannot assure whether there is any peculiarity in HIV‐infected patients compared to other cohorts of sedentary vs active individuals, as comparison between them is lacking. Actually, when it comes to HIV‐infected patients, little evidence on the effects of exercise on vascular function exists—we could only find a single cross‐sectional study showing that arterial compliance was greater in fit vs unfit HIV‐infected individuals and a recent randomized clinical trial, with a small sample size, indicating that short‐term aerobic exercise and folinic acid supplementation improve vascular reactivity in this population . Therefore, we have extended the current knowledge by originally demonstrating that not only macrovascular function, but also angiogenesis and, to a certain extent, antioxidant activity might be favored in patients that underwent regular physical training.…”

The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis

“…The studies were published between 1999 [ 36 , 37 , 38 ] and 2020 [ 39 ], and their characteristics are shown in Table 1 . Twelve studies were performed in the United Kingdom [ 27 , 37 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ], six in Australia [ 26 , 28 , 29 , 50 , 51 , 52 ], five in the Netherlands [ 53 , 54 , 55 , 56 , 57 ], three in Canada [ 58 , 59 , 60 ], three in China [ 38 , 39 , 61 ], and one each in Italy [ 62 ], Brazil [ 63 ], USA [ 64 ], Belgium [ 65 ], Turkey [ 66 ], Greece [ 67 ] and France [ 36 ].…”

“…Most studies were parallel RCTs [ 26 , 27 , 36 , 39 , 40 , 41 , 44 , 45 , 48 , 49 , 50 , 52 , 54 , 56 , 57 , 59 , 60 , 61 , 62 , 63 , 64 , 66 , 67 ] but 13 were crossover RCTs [ 28 , 29 , 37 , 38 , 42 , 43 , 46 , 47 , 51 , 53 , 55 , 58 , 65 ]. The number of participants ranged from 11 [ 63 ] to 528 [ 52 ].…”

“…Most studies were parallel RCTs [ 26 , 27 , 36 , 39 , 40 , 41 , 44 , 45 , 48 , 49 , 50 , 52 , 54 , 56 , 57 , 59 , 60 , 61 , 62 , 63 , 64 , 66 , 67 ] but 13 were crossover RCTs [ 28 , 29 , 37 , 38 , 42 , 43 , 46 , 47 , 51 , 53 , 55 , 58 , 65 ]. The number of participants ranged from 11 [ 63 ] to 528 [ 52 ]. Eight studies included healthy participants [ 29 , 36 , 37 , 38 , 47 , 53 , 55 , 62 ], but most studies involved patients with various diseases, e.g., different types of cardiovascular diseases [ 27 , 40 , 41 , 42 ,…”