ARTICLE
Auteur(s) : Ragnar
Rylander1, Tommi Tallheden2, Jürgen
Vormann3
1BioFact Environmental Health Research Center,
Lerum
2Department of Clinical Chemistry, Skene Hospital,
Skene, Sweden
3Institute for Prevention and Nutrition,
Ismaning, Germany
The acid-base balance in the body is of importance for mineral
homeostasis. The reabsorbtion of calcium and magnesium in the renal
tubuli is influenced by the acidity or the urine. This has been
demonstrated for calcium in an intervention study under carefully
controlled conditions regarding intake of different nutrients [1].
Urinary calcium was measured in test persons before and during a
controlled supply of protein, a major inducer of acid conditions
due to its sulphurous metabolites [2]. When the protein intake was
doubled, the urinary excretion of calcium increased and when sodium
hydrogen carbonate (70 mEq) was given, the excretion
decreased, even at a continued high level of protein intake. The
urinary excretion of magnesium is also related to acid-base
conditions [3] but no intervention studies have been reported.
A commonly used marker of acid load is the net acid excretion
(NAE) in the urine [2]. The analysis of NAE is quite complicated
and time consuming.
Many of the studies on acid-base balance reported previously
have been performed under laboratory conditions with control of
dietary intake of minerals and food items that may influence the
acid-base balance. Although important mechanistic information can
be obtained through these means, the applicability is uncertain for
a public health scenario where dietary intakes are not controlled
for.
The present study was undertaken among healthy subjects in their
normal environment without restrictions on dietary intakes to
evaluate 1) if intervention with tablets with a base-promoting
content would increase the basic load, and 2) if the intervention
would affect the urinary excretion of calcium and magnesium.
Material and methods
A renewed analysis was carried out using data from a population
study that had not previously been analysed [3]. The aim was to
evaluate the possibility of using urea as a proxy for acid
conditions in terms of net acid excretion (NAE).
For the intervention study healthy subjects were recruited
through advertising. Inclusion criteria were age 50-65 and
without any serious disease. Exclusion criteria were medication for
heart disease or blood pressure. The subjects gave informed consent
and the study was approved by the Ethical Committee in West Sweden.
There were considerable problems recruiting subjects to the study,
probably because of the absence of monetary compensation for the
rather tedious collection of urine.
The tablets contained potassium hydrogen carbonate
(KHCO3), and chloride (KCl) as a placebo. They were
randomly given to the subjects. The composition was not known to
the subjects or the investigators. The subjects took 2 tablets
3 times daily for 7-10 days which corresponded to a daily
potassium dose of 30 mEq. The characteristics of the subjects
taking the different categories of tablets are shown in table 1.
The proportion of females was slightly higher in the group
receiving K hydrogen carbonate. The average age in the groups was
very similar.
Before and after the intervention 24 h urine samples were
collected. The amount of calcium was analysed using an ion
detection instrument (Beckman Coulter UniCel DxC 800 synchron
Clinical System, Sweden). Magnesium concentrations were determined
using a time related endpoint method reading the absorbance and
urea using an enzyme time reaction method. All analyses were
performed in a hospital accredited laboratory (Borås, Sweden).
Blood pressure was recorded before and after the intervention in
19 of the 31 subjects. Two persons considered the tablets
too large and discontinued the study.
Differences between the groups were evaluated using the
Mann-Whitney test or the chi2 test. Relationships
between parameters were tested using the Spearman test.
A p-value of 0.05 was considered statistically
significant.
Table 1 Gender and age characteristics of the study
group.
|
Tablet
|
n
|
% females
|
Age years (mean)
|
|
KHCO3
|
17
|
78
|
62
|
|
KCl
|
14
|
57
|
61
|
Results
The results from the new analysis of the material from the
population study on the relation between the urinary excretion of
NAE and urea is illustrated in figure 1. There was a close
relationship (r2 = 0.718, p = 0.0001). Urea was thus
used as a proxy for acid conditions in the intervention study.
Before the intervention there was a significant relation between
the excretion of urea and the excretion of calcium (r2 =
0.478, p = 0.008) and magnesium (r2 = 0.367, p = 0.046)
when the two groups receiving KHCO3 and KCl were
amalgamated. There was also a significant relation between the
excretion of magnesium and calcium (r2 = 0.606, p <
0.001).
Table 2 shows the changes in urinary
excretion of urea, calcium and magnesium in relation to the
different tablets given in the intervention.
In the group receiving the active tablet, there was a
significant decrease in the average excretion of urea (p = 0.037)
and 13 out of 18 subjects decreased their urea secretion.
In the placebo group the corresponding numbers were 4 out of
13 (p = 0.033, chi2 test). This illustrates that
the KHCO3 tablet had an acid reduction effect but for
some people, their normal nutritional habits overcame this
effect.
Figure 2
illustrates the relation between the changes in urea and calcium
and magnesium levels in the group receiving KHCO3.
There was a significant relationship for calcium (p = 0.016) but
not for magnesium (p = 0.126). Similar relations were found for the
group receiving KCl (p = 0.079 and 0.024). If the groups were
amalgamated, the relationships were p = 0.008 for calcium and
p = 0.046 for magnesium.
Table 3 shows the difference in
systolic and diastolic blood pressure after the intervention.
There was a decrease in systolic and diastolic blood pressure
after the intervention. There was no difference between the groups
taking potassium hydrogen carbonate or chloride.
Table 2 Urinary excretion of urea, calcium and
magnesium (mmol/24 h) before and after administration of
tablets containing potassium hydrocarbonate or chloride.
|
Urea
|
Calcium
|
Magnesium
|
|
Tablet
|
Before
|
After
|
Before
|
After
|
Before
|
After
|
|
KHCO3
|
360 (89)
|
326 (99)*
|
3.4 (1.2)
|
3.4 (1.5)
|
3.9 (1.8)
|
4.4 (2.1)
|
|
KCl
|
396 (102)
|
439 (102)
|
4.9 (2.2)
|
4.7 (1.3)
|
4.0 (1.5)
|
4.2 (1.6)
|
Table 3 Systolic and diastolic blood pressure (BP)
before and after treatment with tablets containing potassium
hydrocarbonate or chloride.
|
Systolic BP (mmHg)
|
Diastolic BP (mmHg)
|
|
n
|
Before
|
After
|
p
|
Before
|
After
|
p
|
|
19
|
132.1 (17.5)
|
122.9 (20.0)
|
0.003
|
79.1 (9.2)
|
74.6 (7.5)
|
0.018
|
Discussion
The major results from the study were:
- – a decrease in the excretion of urea related to
decreases in the secretion of calcium and magnesium irrespectively
of the intervention;
- – a decrease in systolic as well as diastolic blood
pressure after administration of the tablets.
There are certain shortcomings in the study. The number of
subjects is fairly small due to the recruitment problems. In spite
of this, significant differences which support previous results
were found. The subjects studied are not representative of the
population in general – none of the subjects was a smoker. This
reflects the selection process in studies of this kind, where
voluntary recruitment favours the inclusion of health conscious
persons. The parameters studied are, however, related to basic
physiological functions and the results should thus be applicable
to the population in general. An advantage in the study is the use
of an elderly population sample as renal function which regulates
uptake of minerals is reduced with age [4]. Urea is not an exact
mirror of acid conditions – if meat is consumed the excretion of
urea increases but if vegetables are consumed at the same time,
there is no effect on the acid-base balance. NAE is a better
indicator of acid conditions but such measurements could not be
performed due to technical limitations.
In some subjects the excretion of urea increased in spite of the
administration of the base-promoting tablet. There was no
difference in mean values of excreted calcium and magnesium between
the two groups, although there was a significant relationship
between the urea excretions. The reason for this is probably due to
variations in the diet - there were no dietary restrictions for the
participants and the effect induced by the tablet was thus masked
by normal variations in the daily nutritional intake, in some cases
leading to a urea reduction also in the placebo group.
Overall the results show a relation between the changes in
urinary excretion of urea and calcium and magnesium. This confirms
the results from a previous laboratory study on calcium [4] and
supports the hypothesis that the acid-base balance is important for
mineral homeostasis among subjects consuming their regular daily
diet without laboratory induced restrictions. Regulation of acid
conditions could thus be a tool for treatment of mineral
deficiency.
The decrease in blood pressure after administration of tablets
containing potassium supports earlier findings using potassium
chloride and citrate [5-7] and also demonstrated an effect of K
hydrocarbonate. As no control tablet was included it cannot be
excluded that part of the decrease was due to habituation of the
subjects to the blood pressure recording procedure. On the other
hand, the measurements were made on persons most of whom were
familiar with the procedure and an appropriate resting period was
applied. It is thus unlikely that all of the effect is due to
habituation. In a previous intervention study a mineral water with
a high level of potassium also caused a decrease in blood pressure
[8]. Should the beneficiary effect of this dose of potassium be
proven in future studies, this opens an interesting possibility for
medication in subjects with only slightly elevated blood
pressure.
In conclusion, the results support a relation between acid
conditions in the body and an increased urinary secretion of
magnesium and calcium. Regulation of acid-base conditions are thus
an alternative for reducing calcium and magnesium deficiency.
Intervention with potassium caused a decrease in systolic and
diastolic blood pressure. This finding should be further explored
with the possibility of providing an alternative for treatment of
moderately increased blood pressure.
Disclosure
R. Rylander received an unconditional research grant from Protina.
T. Tallheden has no disclosures. J. Vormann is head of the
Institute for Prevention and Nutrition which is supported by
Protina GmbH.
Acknowledgments
The authors are grateful to the financial support from
Ekhagastiftelsen, the Wilhelm and Martina Lundgren Research
Foundation, Sweden and Protina GmbH, Germany who also supplied the
different tablets used in the intervention.
References
1 Lutz J. Calcium balance and acid-base status of women as
affected by increased protein intake and by sodium bicarbonate
ingestion. Am J Clin Nutr 1984; 39: 281-8.
2 Remer T. Influence of nutrition on acid-base balance –
metabolic aspects. Eur J Nutr 2001; 40: 214-20.
3 Rylander R, Remer T, Berkemeyer S,
Vormann JJ. Acid-base status affects renal magnesium losses in
healthy, elderly persons. J Nutr 2006; 136: 2374-427.
4 Berkemeyer S, Vormann J, Günther L,
Rylander R, Frassetto LA, Remer T. Renal net acid
excretion capacity is comparable in prepubescence, adolescence and
young adulthood, but is reduced with aging. Am J Ger Soc 2008; 56:
1442-8.
5 Gu D, He J, Duan X, Whelton PK. Effect of
potassium supplementation on blood pressure in Chinese: a
randomised, placebo-controlled trial. J Hypertens 2001; 19:
1325-31.
6 He FJ, Markandu ND, Coltart R, Barron J,
MacGregor GA. Effect of short-term supplementation of
potassium chloride and potassium citrate on blood pressure in
hypertensives. Hypertension 2005; 45: 571-4.
7 Naismith DJ, Braschi A. The effect of low dose
potassium supplementation on blood pressure in apparently healthy
volunteers. Br J Nutr 2003; 90: 53-60.
8 Rylander R, Arnaud MJ. Mineral water intake reduces
blood pressure among subjects with low urinary magnesium and
calcium levels. BMC J Public Health 2004; 4: 56-65.
|
Version imprimable
Version PDF
