Fasting-Induced Natriuresis and SGLT: A New Hypothesis for an Old Enigma

Abstract

For years, physicians and scientists were enthralled by the enigmatic phenomenon of fasting-associated diuresis and natriuresis and their reversal by feeding. This abrupt response is most prominent in obese and hypertensive individuals, and if repeated once and again may lead to the attenuation of blood pressure and improve insulin sensitivity. The mechanisms involved in early natriuresis and diuresis remain speculative as the renin-angiotensin-aldosterone axis and natriuretic peptides are initially suppressed. Based on gained insight using sodium-glucose transporter 2 (SGLT-2) inhibitors, herein, we propose a role for enhanced post-prandial proximal tubular sodium uptake, mediated by increased glucose-sodium co-transport, as daily filtered glucose increases, and reduced sodium uptake when glucose reabsorption diminishes. This phenomenon might be more pronounced in diabetics due to prolonged post-prandial hyperglycemia and intense SGLT-driven transport. Our hypothesis may also provide a physiologic basis for fasting-related reduced blood pressure in hypertension. This theory deserves challenging by experimental and clinical studies.

Prolonged Fasting as a Cause of Deep Vein Thrombosis: A Case Report

“…Complex physiologic processes occurring with fasting have been hypothetically suggested as a cause of observed increased diuresis and potential resulting dehydration. 10 The decrease of glucose intake impairs sodium reabsorption as glucose-sodium cotransport in renal proximal tubules is inhibited. This ensued natriuresis is not compensated enough by the distal tubular sodium reuptake and then explains resulting osmotic diuresis and subsequent dehydration.…”

Potential Effects of Prolonged Water-Only Fasting Followed by a Whole-Plant-Food Diet on Salty and Sweet Taste Sensitivity and Perceived Intensity, Food Liking, and Dietary Intake

“…It is unknown if fasting affects oral microbiota but there is evidence that a "vegan" diet affects oral microbiota diversity, structure, and relative abundance [26]. Natriuresis is a well-known consequence of fasting, particularly in obese or hypertensive individuals [27], but this effect is unlikely to be related to the increased salty taste sensitivity and perceived intensity observed after fasting as there is evidence that sodium balance is not regulated by taste function [28].…”

Fasten – ein potentes Therapeutikum der Moderne

“…Mehrere Signalwege sind für eine Blutdrucksenkung verantwortlich. Neben einer vermehrten Diurese und Natriurese – unter anderem aufgrund erhöhter Rezeptorsensitivität gegenüber natriuretischem Peptid und Insulin 24 – kommt es, durch vermehrte Freisetzung von BDNF, zu einer erhöhten parasympathischen Aktivierung 1 .…”