Epilepsy

Epilepsy is fundamentally a disorder of brain energy metabolism, where a failure to sustain the high metabolic rate of neurons leads to an excitotoxic state. 2 Peat argued that the core pathology is not a primary electrical misfiring, but a cellular energy crisis where excitation outpaces the cell's ability to produce energy, leading to a destructive cascade. 2 This excitotoxicity, in its simplest sense, occurs when an excitatory transmitter like glutamate acts on a cell whose energetic reserves are inadequate to sustain the provoked activity. 5 The condition is closely tied to hypothyroidism and estrogen dominance, which create the physiological preconditions—such as edema and hyponatremia—that lower the seizure threshold. 2

The metabolic vulnerability in epilepsy is heavily influenced by systemic hormonal and mineral imbalances. Hypothyroid individuals tend to lose sodium easily, while unopposed estrogen increases water retention without equivalent sodium retention, creating a state of dilutional hyponatremia that directly predisposes brain cells to swell and seize. 2 This is why neurologists historically used excessive water intake or hyperventilation as diagnostic tools; both cause cellular overhydration and a loss of carbon dioxide, which is a crucial regulator of neuronal stability. 2 Peat emphasized that carbon dioxide deficiency, often caused by hyperventilation, reduces oxygen delivery to the brain, constricts blood vessels, and impairs the Krebs cycle's ability to consume excitatory amino acids like glutamate and aspartate. 2 The drug acetazolamide, which retains carbon dioxide by inhibiting carbonic anhydrase, has been effective in preventing seizures, asthma, and altitude sickness precisely because it corrects this deficiency. 7

The excitotoxic cascade itself is a self-amplifying process driven by the release of polyunsaturated fatty acids (PUFAs) and the loss of ionic control. Once a cell's energy production fails, calcium enters the cell, potassium leaves, and enzymes are activated that produce free fatty acids like linoleic and arachidonic acid, along with prostaglandins and free radicals. 2 These PUFAs cause mitochondrial damage and edema, further impairing energy production and making the cell more excitable. 8 Peat noted that protein kinase C, promoted by unsaturated fats and estrogen, facilitates the release of excitatory amino acids, while estrogen also stimulates acetylcholine release and free radical production, creating a bias toward increased excitation. 3 In contrast, saturated fatty acids do not have these damaging effects, and the ketone bodies produced by a ketogenic diet—such as beta-hydroxybutyrate—are protective both by providing an alternative energy source for damaged mitochondria and by acting as a structural analog to the inhibitory neurotransmitter GABA. 8

Therapeutic intervention, in Peat's framework, centers on restoring energy production and blocking the excitatory cascade at multiple points. The brain itself is a major steroid-forming organ, producing pregnenolone and progesterone, which have a quieting, anti-excitatory effect and raise the seizure threshold. 2 Progesterone opposes estrogen's excitatory actions and has been used successfully to reduce or replace anticonvulsant drugs, which Peat condemned as both neurotoxic and teratogenic. 2 However, when a person is resistant to progesterone and requires extremely large doses, it typically indicates that the liver is failing to detoxify estrogen and excitatory substances, necessitating support for thyroid function and liver glycogen storage through a diet rich in sugar (such as orange juice) and gelatin, while avoiding the excitatory amino acids cysteine, tryptophan, glutamic acid, and aspartic acid. 2 Adequate intake of the alkaline minerals—sodium, potassium, calcium, and magnesium—from sources like fruit, milk, and well-cooked greens is also critical for stabilizing the nervous system and preventing the intestinal irritation that can promote seizures by increasing systemic nitric oxide and sodium loss. 2