Ketosis

Ketosis is a metabolic state that Ray Peat argued activates the stress system when the body is forced to produce its own ketone bodies due to insufficient dietary sugar. 1 Peat explained that turning on the process of making ketones means you aren't getting enough glucose or fructose, which triggers cortisol production with its chronic harmful and developmental effects. 1 Danny Roddy has elaborated that this state mimics the stress metabolism, noting that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress, and that becoming a "fat burner" through carbohydrate restriction is a hallmark of aging and disease. 3 The mechanism involves a short-term increase in adrenaline to liberate free fatty acids, followed by a long-term rise in cortisol and other pituitary hormones that increase the rate of lipolysis, slowing the metabolism and bringing systemic renewal to a halt. 3

A central physiological defect of endogenous ketosis is the suppression of oxidative metabolism and carbon dioxide production. Roddy has pointed out that the oxidation of free fatty acids provides far less carbon dioxide than the oxidation of glucose, and that carbon dioxide is a basic anti-stress factor and a critical cofactor for the assimilation of fat-soluble vitamins. 3 This shift in fuel oxidation also alters the cellular redox state. Peat described how carbon dioxide acts as a cardinal adsorbent that pulls electrons out of the system, shifting the NAD+/NADH ratio toward the oxidized side. 6 Without sufficient carbohydrate intake, the organism mounts a chronic adaptive stress response that becomes less efficient over time, leading to what Roddy characterized as a hibernation-like state for humans, measurable by a declining resting pulse rate and body temperature. 2

Despite these criticisms, Peat and Georgi Dinkov acknowledged that certain ketone bodies and related molecules have protective, GABAergic properties that explain the anti-seizure effects of ketogenic diets. Peat noted that beta-hydroxybutyrate is structurally close to GABA, and that other close analogs like gamma-hydroxybutyrate act as regulatory substances rather than mere energy sources. 2 Dinkov emphasized that these anti-epileptic effects are specific to the type of fat consumed; they occur with short-chain saturated fatty acids and long-chain saturated fats, but not with polyunsaturated vegetable oils high in linoleic acid. 5 This suggests that the benefit is not from ketosis itself, but from the type of fat being used. 5 Peat further distinguished that dietary precursors which are partly formed ketones are "equivalent to sugar, only better," whereas endogenous production driven by sugar deprivation is harmful. 1

The therapeutic application of ketone bodies extends to mitochondrial repair. Peat cited evidence that providing ketone bodies can replace genetically defective mitochondria with genetically normal ones, and that medium-chain triglycerides can improve mental functions in Alzheimer's patients, a condition he described as "diabetes of the brain" due to slow glucose and oxygen utilization. 2 However, the metabolic context remains crucial. Roddy and Dinkov observed that many on ketogenic diets experience increased muscle soreness due to the conversion of glucose to lactic acid in the absence of sufficient carbon dioxide, a phenomenon akin to the Warburg effect. 5 Peat noted that diabetics, who are often described as unable to use glucose, typically have increased lactate in their blood, indicating wasteful glucose metabolism alongside fat oxidation. 2 The elevation of free fatty acids and the reliance on lipolysis are thus seen not as a metabolic advantage, but as a compensatory stress response that precedes hyperglycemia. 3