The effects of capsaicin and tea on sodium and water homeostasis as measured by osmoregulation and blood pressure.

Hyponatremia, defined as a plasma sodium concentration <135 mmol/L, is the most
common electrolyte disorder found worldwide. Hyponatremia is independently
associated with increased morbidity and mortality in various groups of patients
and in the general population. Attention deficits, gait disturbances, falls,
fractures and osteoporosis are all important consequences of chronic
hyponatremia. Thus, disturbed osmoregulation leading to hyponatremia has
important impact on general health. The pathophysiology of hyponatremia however
is incomplete. Generally, excess of water is regarded as the main cause of a
low serum sodium concentration. Central and local compensation mechanisms
become more active when a change of sodium concentration or plasma osmolality
is detected. The reason why some subjects, despite these compensation
mechanisms, still develop hyponatremia is largely unknown. Our group just
discovered a significant association between plasma sodium concentration and
synonymous single nucleotide polymorphism (SNP) in the TRPV1 gene. TRPV1 is a
protein that can be activated by its ligand capsaicin (i.e., the active purgent
of red hot chili). Modulation of TRPV1 expression and activation by capsaicin
administration is hypothesized to induce hyponatremia. Flavonoids include a
huge group of naturally occurring organic compounds and seem to exhibit effects
on sodium and water homeostasis as well. Animal studies have demonstrated that
flavonoids down regulating the epithelium sodium channel (ENaC) in the kidney,
preventing sodium reabsorption and stimulating natriuresis as a consequence.
Consumption of flavonoids may put subjects at risk of development of
hyponatremia. To our knowledge, the effects of both capsaicin and tea on
hydration status have not been studied in human subjects so far.

1. To assess whether acute TRPV1 activation by capsaicin or ENaC down
regulation by flavonoids modulate osmoregulation in healthy subjects
2. To assess whether capsaicin and flavonoids affect blood pressure

A single-blinded randomized cross-over interventional study

Capsaicin and tea (flavonoids) will be administered to examine the effects on
osmoregulation, kidney function and blood pressure with and without a
concurrent water load (WL). For the WL, 20mL/kg water has to be ingested in 20
minutes. For the WL warmish water will be used.

Nature and extent of the burden and risk associated with participation, benefit
and group relatedness: When our hypotheses will be confirmed by this study,
further knowledge about the relation between capsaicin, activated TRPV1,
flavonoids, ENaC downregulation, disturbed osmoregulation and sodium
concentration in humans will be provided. Better understanding of
pathophysiological mechanisms in vivo are necessary in order to provide support
for new therapeutic strategies and epidemiological approaches. Participating in
this research project will not lead to personal benefit or to group level
benefit. Little to no burden is expected when participating in this study.
Subjects will visit our research department 4 times, totaling 19 hours. During
these visits venous blood will be drawn totaling approximately 158 mL. Subjects
will be asked to collect 24-h urine thrice. This study aims to unravel one of
the pathophysiological mechanisms leading to hyponatremia. At the very long run
various groups of patients might benefit from the results, particularly
patients at risk for hyponatremia, such as elderly subjects, subjects using
diuretics, subjects with heart failure or renal failure.