Original article
Alkalinization with potassium bicarbonate improves glutathione
status and protein kinetics in young volunteers during 21-day bed rest
Q2
Q1
Gianni Biolo
a, *
, Filippo Giorgio Di Girolamo
a
, Martina Heer
b
, Mariella Sturma
a
,
Sara Mazzucco
a
, Francesco Agostini
a
, Roberta Situlin
a
, Pierandrea Vinci
a
,
Mauro Giordano
c
, Judith Buehlmeier
d
, Petra Frings-Meuthen
d
, Filippo Mearelli
a
,
Nicola Fiotti
a
a
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
b
Department of Nutrition and Food Science, Nutrition Physiology, University of Bonn, Bonn, Germany
c
Department of Medical, Surgical, Neurological, Metabolic and Geriatrics Sciences, Second University of Naples, Naples, Italy
d
Institute of Aerospace Medicine, German Aerospace Center (DLR), K€ oln, Germany
article info
Article history:
Received 21 June 2017
Accepted 6 April 2018
Keywords:
Alkalinization
Protein kinetics
Glutathione status
Experimental bed rest
Oxidative stress
summary
Background & aims: Physical inactivity is associated with lean body mass wasting, oxidative stress and
pro-inflammatory changes of cell membrane lipids. Alkalinization may potentially counteract these al-
terations. We evaluated the effects of potassium bicarbonate supplementation on protein kinetics,
glutathione status and pro- and anti-inflammatory polyunsaturated fatty acids (PUFA) in erythrocyte
membranes in humans, during experimental bed rest.
Methods: Healthy, young, male volunteers were investigated at the end of two 21-day bed rest periods,
one with, and the other without, daily potassium bicarbonate supplementation (90 mmol d
1
), ac-
cording to a cross-over design. Oxidative stress in erythrocytes was evaluated by determining the ratio
between reduced (GSH) and oxidized glutathione (GSSG). Glutathione turnover and phenylalanine ki-
netics, a marker of whole body protein metabolism, were determined by stable isotope infusions.
Erythrocyte membranes PUFA composition was analyzed by gas-chromatography.
Results: At the end of the two study periods, urinary pH was 10 ± 3% greater in subjects receiving po-
tassium bicarbonate supplementation (7.23 ± 0.15 vs. 6.68 ± 0.11, p < 0.001). Alkalinization increased
total glutathione concentrations by 5 ± 2% (p < 0.05) and decreased its rate of clearance by 38 ± 13%
(p < 0.05), without significantly changing GSH-to-GSSG ratio. After alkalinization, net protein balance in
the postabsorptive state improved significantly by 17 ± 5% (p < 0.05) as well as the sum of n-3 PUFA and
the n-3-to-n-6 PUFA ratio in erythrocyte membranes (p < 0.05).
Conclusions: Alkalinization during long-term inactivity is associated with improved glutathione status,
anti-inflammatory lipid pattern in cell membranes and reduction in protein catabolism at whole body
level. This study suggests that, in clinical conditions characterized by inactivity, oxidative stress and
inflammation, alkalinization could be a useful adjuvant therapeutic strategy.
© 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
1. Introduction
Acid-base balance has important regulatory effects on body
protein kinetics. The consequences of alkalosis and acidosis on
protein metabolism have been extensively described in health and
disease conditions [1,2]. In experimental models in vitro, increasing
extracellular pH enhanced protein anabolism and inhibited protein
catabolism [3e5]. In hyperventilated head trauma patients, respi-
ratory alkalosis increased muscle protein synthesis up to 33% [6].
On the contrary, metabolic acidosis observed in chronic kidney
Abbreviations: absolute synthesis rate (ASR), ambulatory period (AMB); area-
under-the-curve (AUC), bed rest with standard nutrition (BR); bed rest with stan-
dard nutrition plus potassium bicarbonate (BRKB), chronic kidney disease (CKD);
fat mass (FM), fractional synthesis rate (FSR); reduced glutathione (GSH), gluta-
thione clearance (GSH clearance); oxidized glutathione (GSSG), high density lipo-
protein (HDL); lean body mass (LBM), low density lipoprotein (LDL);
polyunsaturated fatty acid (PUFA), reactive oxygen species (ROS).
* Corresponding author. ASUITs, Department of Medical, Surgical and Health
Sciences, University of Trieste, Strada di Fiume, 447 34149 Trieste, Italy.
E-mail address: biolo@units.it (G. Biolo).
Contents lists available at ScienceDirect
Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu
https://doi.org/10.1016/j.clnu.2018.04.006
0261-5614/© 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Clinical Nutrition xxx (2018) 1e8
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Please cite this article in press as: Biolo G, et al., Alkalinization with potassium bicarbonate improves glutathione status and protein kinetics in
young volunteers during 21-daybed rest, Clinical Nutrition (2018), https://doi.org/10.1016/j.clnu.2018.04.006