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.
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.
University of Welfare Sciences, Kasiwara, Osaka, 582-0026, Japan; RIKEN Center for Life Science Technologies, Kobe, Hyogo, 650-0047, Japan; Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Sanae
S
Fukuda
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan; Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan.
Hidenori
H
Koyama
Department of Virology, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
Kazuhiro
K
Kondo
Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan; Center for Drug & Food Clinical Evaluation, Osaka City University Hospital, Osaka, 540-0051, Japan.
Hisako
H
Fujii
College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, 525-8577, Japan.
Yoshinobu
Y
Hirayama
Inoue Hospital, Suita, 564-0053, Japan.
Tsutomu
T
Tabata
Ohno Memorial Hospital, Osaka, 550-0015, Japan.
Mikio
M
Okamura
Shirasagi Hospital, Osaka, 546-0002, Japan.
Tomoyuki
T
Yamakawa
Okada Clinic, Osaka, 543-0056, Japan.
Shigeki
S
Okada
Kumamoto University School of Pharmacy, Kumamoto, 862-0973, Japan.
Sumio
S
Hirata
Nagoya University School of Medicine, Nagoya, 466-8550, Japan.
Hiroshi
H
Kiyama
Department of Medical Science on Fatigue, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Osami
O
Kajimoto
RIKEN Center for Life Science Technologies, Kobe, Hyogo, 650-0047, Japan; Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Yasuyoshi
Y
Watanabe
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Masaaki
M
Inaba
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Yoshiki
Y
Nishizawa
D000328:Adult; D000368:Aged; D019587:Dietary Supplements; D004311:Double-Blind Method; D005221:Fatigue / Q000150:complications / Q000628:therapy*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D006435:Renal Dialysis
D010919:Placebos