Salt: The paradoxical philosopher's stone of autonomic medicine

Sodium chloride, or common table salt, for millennia has played a prominent role in human affairs. Salt is also a key molecule for regulating intravascular fluid volume in patients with orthostatic disorders. In this first article of a special issue of the journal focusing on salt and the autonomic nervous system, the historical and physiologic significance of salt is reviewed, highlighting its importance to society and to medicine. The relevance of salt both for civilization and for autonomic physiology penetrates into nearly every aspect of life and health. Replacing salt that has been depleted or administering salt to expand intravascular volume is considered standard treatment for patients with orthostatic hypotension and syndromes of orthostatic intolerance. The potential longterm effects of added salt, including effects unrelated to intravascular volume, have been insufficiently studied in patients with autonomic disorders. A salient concern is the potential increased risk of developing hypertension. Underappreciated aspects of salt include its ability to increase anxiety and through nonosmotic mechanisms to contribute to local tissue inflammation. Salt may be either salubrious or detrimental, or possibly both at the same time, depending on the clinical conditions. Reconciling these opposite effects in clinical practice requires weighing benefits against potential risks, assessing what is known alongside what is uncertain, and titrating treatment decisions to the particular needs of each individual patient. •Salt has profoundly shaped human history, including diet and medicine.•Salt improves orthostatic tolerance but also increases risk of hypertension.•Although recommended by consensus, randomized controlled studies have not been done.•Salt also affects immune function, psychological state, and gut microbiota.•Longterm treatment of POTS should include blood pressure monitoring.