Effects of nutritional supplementation on fatigue, and autonomic and immune dysfunction in patients with end-stage renal disease: a randomized, double-blind, placebo-controlled, multicenter trial

Abstract

Background: Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis.

Methods: Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography.

Results: Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance.

Conclusions: Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis.

Fig 1. Flowchart of enrollment of randomized control study.

Fig 2. Changes in HRV; LF/HF value (0–4 and 0–12 weeks).

LF/HF ratio. Error bars represent the standard error of the mean. Differences of changes in LF/HF ratio between the nutritional drink and placebo groups were determined via the Mann–Whitney test. The baseline LF/FH did not differ significantly between the groups (Z = −0.87, P = 0.39).

Fig 3. Changes in HHV6 and 7 reactivation following nutritional supplementation in patients with ESRD (0–12 weeks).

Differences of changes in the number of copies of (a) HHV6 and (b) HHV7 DNA were determined via the Mann–Whitney test by treatment groups, placebo and nutritional drink (HHV6, Z = −6.08, P = 0.54 and Z = −0.18, P = 0.86 and HHV7, Z = −0.62, P = 0.54 and Z = −2.43, P = 0.016, respectively). We performed the statistical analysis for the samples that exceeded the detection limits, thereafter, the number of participants with these parameters were smaller than in the total samples (HHV6, 23 in the placebo and 22 in the nutritional drink groups, and HHV7, 50 in the placebo and 60 in the nutritional drink groups). Error bars represent the standard error of the mean.