The VITAH Trial—Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial

Abstract

End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013–March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. Trial Registration: ClinicalTrials.gov, NCT01774812.

Heart Rate Variability and Long Chain n-3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study

“…Although only 2 patients presented SDNN under 50 ms in the present study, the mean 24 h SDNN of this study population was 84 ms; considered to be moderately depressed. This finding is consistent with other published studies reporting depressed HRV in haemodialysis patients [ 6 , 8 , 18 , 38 , 40 , 41 , 42 , 43 ]. Effects of medication on HRV should be considered in this poly-medicated patient population.…”

“…This study confirms previous reports that HRV is substantially reduced in haemodialysis patients compared to healthy controls [36,37] and extends these findings by demonstrating consistently that time-domain and frequency-domain HRV parameters were significantly lower in haemodialysis patients compared to age-, sex-and BMI-matched healthy controls. Patients in this study also had SDNN measurements amongst the lowest reported in comparison to other haemodialysis cohorts [6,8,18,38]. This might be related to the fact that these were patients that recently started haemodialysis (measurements taken between 6 and 10 weeks of commencing treatment).…”

Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso

“…Entretanto, só houve elevação nesta relação nos indivíduos que permaneceram com vitamina D sérica insuficiente, mesmo após suplementação intensiva por seis semanas. 36 De forma semelhante, este ensaio encontrou proteção vagal após a suplementação da vitamina D, pela elevação significativa do tônus parassimpático. Adicionalmente, esses achados se corroboraram, de forma consistente, pela redução significativa do tônus simpático.…”

Functional Nutrients for Epilepsy

“…Because vitamin D3 has versatile therapeutic efficacies on cardiovascular diseases [142], vitamin D3 may have an impact on SUDEP [143]. Although there is no direct evidence demonstrating a possible role for vitamin D in SUDEP prevention, one group has reported that vitamin D supplementation can modulate HRV [144,145,146,147], which is frequently lower in patients with drug-refractory epilepsy, a group at high risk of SUDEP [148,149]. This raises the possibility that vitamin D may have therapeutic benefits for the prevention of SUDEP.…”