Vasopressin

Vasopressin, also known as antidiuretic hormone (ADH), is a pituitary hormone that Ray Peat identified as a central mediator of stress-induced water retention, sodium loss, and vascular dysfunction. 2 Peat argued that ADH causes sodium loss, water retention, vascular leakiness, and constriction of arterioles, increasing blood pressure while decreasing the delivery of oxygen to the tissues, and increasing the tendency of blood to clot inappropriately. 1 He described a syndrome of inappropriate ADH secretion, often seen in old people and hospitalized trauma patients, characterized by becoming waterlogged while losing sodium into the urine. 6 This pathological pattern is part of a broader stress cascade involving nitric oxide and estrogen, both of which produce a similar state of cellular swelling and sodium wasting. 6

The regulation of ADH is intimately tied to the steroid hormones and metabolic rate. Peat explained that progesterone and atrial natriuretic peptide (ANP) each help to prevent excessive vascular permeability and to inhibit the secretion of ADH from the pituitary. 1 Conversely, estrogen lowers ANP, increases ADH/vasopressin, and causes water retention and sodium loss. 2 Thyroid hormone, like progesterone, also increases ANP and is essential for regulating sodium and water, with hypothyroid people always tending toward the waterlogged, sodium-losing state. 2 The normal diurnal rhythm of ADH should turn on during sleep to maintain blood volume, but it should fall immediately in the morning; copious daytime urination is acceptable if fluid intake is high, as evaporation accounts for liters per day when the metabolic rate is high. 2

Peat’s therapeutic approach to ADH excess focused on restoring oxidative metabolism and carbon dioxide levels rather than using conventional diuretics, which he considered as poorly founded as mercury-based treatments that simply damage the kidneys. 6 He noted that sodium chloride and sodium bicarbonate have a diuretic action by increasing blood osmolarity and expanding blood volume, which improves kidney perfusion, and that sodium itself can cure many stress conditions involving waterlogging and sodium loss. 2 The underlying regulator of this balance is carbon dioxide, which is produced by proper thyroid function; hypertonic sodium chloride and increased carbon dioxide themselves increase the formation of ANP, which then suppresses ADH. 3 Acetazolamide, which retains carbon dioxide by inhibiting carbonic anhydrase, is used to prevent edema of the lungs and brain, and intracellular acidosis from carbon dioxide decreases the cell’s affinity for water. 5

In the context of heart failure and other degenerative conditions, Peat viewed ADH antagonism as a rational strategy. He noted that drugs to antagonize ADH are available and are sometimes used to treat heart failure, helping to increase sodium retention. 1 However, he emphasized that natural steroids derived from pregnenolone, either progesterone or DHEA, will help with water retention, edema, and heart failure by opposing the entire stress cascade that includes ADH. 4 The stress-induced agents that promote water retention, including ADH, serotonin, aldosterone, and prolactin, are all lowered by thyroid and progesterone. 4 This systems-level view positions ADH not as an isolated target but as one component of a catabolic stress response that is best corrected by restoring efficient energy production and carbon dioxide levels. 2