Can it really be this simple? A ketogenic diet…. or supplements like caprylic acid or medium-chain triglycerides… replace glucose metabolism with β-Hydroxybutyrate and acetoacetate, or ketosis.
In myalgic encephalomyelitis (and multiple sclerosis), the ability to break down amino acids like tryptophan is affected by reduced IDO level. IDO isn’t there because it needs interferons like IFN-beta and IFN-gamma, which are essential building blocks of the immune system, which these diseases reduce. The ketogenic (high-fat, low-carb) diet, or ketone bodies in general, bypass this problem.
Evidence points to an effect on brain handling of amino acids, especially glutamic acid, the major excitatory neurotransmitter of the central nervous system. The diet may limit the availability of oxaloacetate to the aspartate aminotransferase reaction, an important route of brain glutamate handling. As a result, more glutamate becomes accessible to the glutamate decarboxylase reaction to yield gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter and an important antiseizure agent. In addition, the ketogenic diet appears to favor the synthesis of glutamine, an essential precursor to GABA. This occurs both because ketone body carbon is metabolized to glutamine and because in ketosis there is increased consumption of acetate, which astrocytes in the brain quickly convert to glutamine.
The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect.
The extreme hypersensitivity to sound, and the whirlwind of discombobulated sensations that replaces ordinary thought in severe ME, and causes paralysis, is a type of seizure. GABA is a natural anti-seizure agent in the nervous system. This line of thought says that the neurological manifestations of M.E. are due to a metabolic disorder, which is triggered by imbalances in the immune system.
It is well known by the ME community (not ME/CFS) that this disease features abnormalities in cellular energy utilization.
This review article explores the rationale for using the KD and related dietary treatments in neurological disorders outside of epilepsy, and summarizes the clinical experience to date. An underlying theme of such diet-based therapies is that nutrients and metabolic substrates can exert profound effects on neuronal plasticity, modifying neural circuits and cellular properties to enhance and normalize function. At a fundamental level, any disease in which the pathogenesis is influenced by abnormalities in cellular energy utilization – and this implies almost every known condition – would theoretically be amenable to the KD. It is important to acknowledge that much of the data discussed here are preliminary and anecdotal, and hence need to be validated by well-controlled prospective studies. Nevertheless, that diet and nutrition should influence brain function should not be altogether surprising, and there are already abundant clinical and laboratory data linking defects in energy metabolism to a wide variety of disease states (Waldbaum and Patel, 2010; Roth et al., 2011; Schiff et al., 2011). Thus, the potential for interesting and novel applications of the KD and related dietary therapies is almost limitless (Stafstrom, 2004).
The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders
Oxidative stress is the first link in the ME chain, ahead of even STAT-1 inhibition. Oxidative stress in increased by exercise, which brings on post-exertional neuroimmune exhaustion. Radioactive contaminants in the body also lead to free radicals and oxidative stress, since radiation causes radiolysis, the splitting of water into hydrogen and oxygen:
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Ketosis reduces the amount of glutamate available for neurotransmitter usage, and is then available for GABA synthesis. Glutamate as a neurotransmitter causes neural excitability, and the hypersensitivity and paralysis in severe ME, and GABA causes the opposite, neural inhibition:
Availability of neurotransmitter glutamate is diminished when β-hydroxybutyrate replaces glucose in cultured neurons
An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases.
Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases
Here we hypothesize that CNS depressants may promote consciousness recovery by reversing a condition of GABA impairment in the injured brain, restoring the normal ratio between synaptic excitation and inhibition, which is the prerequisite for any transition from a resting state to goal-oriented activities (GABA impairment hypothesis). Alternative or complementary mechanisms underlying the improvement of consciousness may include the reversal of a neurodormant state within areas affected by diaschisis (diaschisis hypothesis) and the modulation of an informative overload to the cortex as a consequence of filter failure in the injured brain (informative overload hypothesis).
Silencing the brain may be better than stimulating it. The GABA effect.