I have dysautonomia. I reread 2006 review by Derrick Lonsdale (1), which Costatini cites. Lonsdale calls attention to high calorie malnutrition. HCM can occur when an individual eats too much sugar, carbohydrates, or fat. Parts of the Krebs cycle are affected. Eg, Thiamine deficiency can ensure, leading to various pathologies.
See also :
The Malnutrition of Obesity: Micronutrient Deficiencies That Promote Diabetes
Lonsdale is considered the guru of thiamine and I know Dr. Costantini is a definite fan! One can only wonder what they might have done as a research team together!
Dr Lonsdale stresses that too many calories with little to no nutritional value overwhelm parts of the Krebs cycle, can induce acquired malnutrition, including low Thiamine and low magnesium. Too much sugar, too much carbohydrate, too much non-nutritious fat -- which the liver can convert to glucose and glycogen.
Areas commonly affected by thiamine deficiency are the mediodorsal thalamic nucleus, mammillary bodies, the periaqueductal gray matter, and the floor of the fourth ventricle, which includes the ocular motor, vestibular nuclei, and the cerebellar vermis.16 Lesions also may involve the fornices, the hippocampus, the area round the third ventricle, the quadrigeminal bodies, and the cortex.17
Deficiency of thiamine affects all organ systems, particularly the cells of the nervous system (e.g., neurons and glia cells, which are supporting cells in the nervous system).19
Thiamine pyrophosphate (TPP), the active form of thiamine, is a required cofactor in two enzyme-mediated carbohydrate metabolism pathways, which are the Kreb’s cycle (also known as the citric acid cycle) and Pentose phosphate pathway. The Kreb’s cycle is a central metabolic pathway that completes the oxidative degradation of monosaccharide (carbohydrate) and other nutrients, such as fatty acids and amino acids, and occurs in the mitochondria of every cell that utilizes oxygen. The diagram in Figure 2 shows the utilization of thiamine (TPP) in the Kreb’s cycle.
There are two main enzymes, pyruvate dehydrogenase complex (PDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) that require thiamine as a cofactor in the Kreb’s cycle. The main function of the pathway is the generation of a molecule called adenosine triphosphate (ATP), which provides energy for numerous cellular processes and reactions.20
A decrease in ATP production in the brain leads to an increase in production of toxic metabolites of dopamine and inhibition of catechol-O-methyl transferase (COMT) activities, which is a vital enzyme for synthesis and breakdown of dopamine in the prefrontal cortex.21,22 Thus, an increase in the level of dopamine may lead to delirium, including hallucinations and delusions.22 In addition, proper functioning of PDH is essential for the production of the neurotransmitter acetylcholine as well as for the synthesis of myelin.20
The citric acid cycle and alpha-KGDH play a role in maintaining the levels of the glutamate, gamma aminobutyric acid (GABA), and aspartate.24,25
And good old vitamin B1 is a cofactor to a zillion energetic reactions. If you burn glucose, you desperately need your thiamine. To quote my old Harrison's Principles of Internal Medicine, 14th Edition (page 2455):
Thiamine is a cofactor of several enzymes, including transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. Thiamine deficiency produces a diffuse decrease in cerebral glucose utilization and results in mitochondrial damage… electron microscopy shows disintegrating mitochondria, chromatin clumping, and swelling of degenerating neurons…consistent with excitotoxicity.
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