Ketosis, salt, and water: novel mechanistic insights into diet and mineralocorticoid metabolism

The association between dietary macronutrient composition and cardiovascular health has been studied extensively for decades. High dietary sodium intake has traditionally been linked with cardiovascular disease and mortality, although recent data suggest that this association may be negligible where mean intake is less than 5g/day. The renin-angiotensin-aldosterone system (RAAS) is a key regulator of circulating blood volume, as well as sodium and potassium homeostasis. Renin production from the renal juxtaglomerular apparatus is stimulated by reduced circulating blood volume, thereby stimulating aldosterone secretion from zona glomerulosa cells of the adrenal cortex. Primary aldosteronism, due to a unilateral aldosterone-producing adenoma (Conn’s syndrome) or bilateral hyperplasia of the glomerulosa, is an important cause of secondary hypertension and has independent associations with cardiovascular disease. In the absence of autonomous aldosterone production, antagonism of the mineralocorticoid receptor is a key therapeutic approach in hypertension and heart disease by lowering blood pressure and improving cardiac remodelling.