Ray mentioned in a few of his articles that a reductive state, characterized by a buildup of sulfhydryl (SH) groups, is a key characteristic hypothyroidism and of many chronic diseases, especially chronic inflammatory states, diabetes, cancer, neurodegenerative conditions, heart disease (CVD), etc.<\/p>\n
https:\/\/raypeat.com\/articles\/articles\/cancer-progesterone.shtml<\/a><\/p>\n “…One of the basic reactions to injury is to shift the cell away from oxidative metabolism to glycolytic metabolism, which is inefficient, but can support cell division. Chemical stains show that during cell division cells are in a reduced state, with abundant sulfhydryl groups<\/span> including reduced glutathione and protein sulfhydryls. This shift in itself increases the formation of active estradiol from estrone<\/strong><\/span>.”<\/p>\n https:\/\/raypeat.com\/articles\/articles\/fatigue-aging-recuperation.shtml<\/a><\/p>\n “…Thyroid<\/span><\/strong> stimulation of oxygen consumption tends to prevent lactic acid production, because it keeps the cytoplasm in a state of relative oxidation, i.e., it keeps the concentration of NAD+ hundreds of times higher than that of NADH. NADH<\/span> is required for the conversion of pyruvate to lactate. It is also the source of reducing potential in many kinds of toxic redox cycling, that<\/span><\/strong> <\/span>generate lipid peroxides, and it maintains the sulfhydryl system<\/span>, involving the balance of reduced glutathione<\/span> (GSH<\/span>) with the sulfhydryl-disulfide system<\/span> of protein bonds, which governs the cell’s electronic state<\/span> and affects its balance of hydrophobicity and hydrophilicity<\/strong><\/span>.”<\/p>\n Conversely, shifting the state away from reduction and towards oxidation has many beneficial effects that are not explainable by a single pathway or mechanism. The study below demonstrates that an intact SH group on the GR receptor is essential for the activation of the GR and thus the stress response\/cascade. Conversely, blocking access to the SH group of the GR by either binding it or oxidizing it into a disulfide group blocks the activation of the GR by known glucocorticoid ligands such as the endogenous cortisol, or synthetic glucocorticoids. Thus, SH binding or oxidizing agents act as “silent” GR antagonists and as such are expected to have a variety of beneficial effects considering that cortisol is (relatively) elevated in virtually all chronic diseases and also in general aging. This is due to the fact that the relative “stress” signalling characterized by ratios such as cortisol\/DHEA, cortisol\/androgens, cortisol\/progesterone increases with disease\/age due to decline of anti-cortisol factors such as DHEA, androgens, progesterone, etc. The study looked specifically at beta-lapachone, a powerful ortho-naphthoquinone, and found it to be such a silent GR antagonist, which probably explains a good deal of the benefits seen from usage of this quinone. However, the mechanism of action is general in nature and suggests that all oxidizing agents capable of oxidizing the SH group of the GR would also have similar anti-cortisol effects. In addition to the role of intact SH group in GR activation, the study also cites other studies demonstrating that intact SH group is crucial for the activation of the estrogen receptor (ER) as well. As such, oxidizing agents are likely to also act as ER antagonists. There is already published evidence demonstrating that vitamin K (a para-naphthoquinone) has anti-estrogenic effects, and the findings of the study below probably explain why. Under the same logic, it is expected that other powerful quinones such as COQ10, idebenone, thymoquinone, emodin, aloe, emodin, methylene blue (MB), etc. would also have anti-cortisol and anti-estrogenic effects. In addition, non-oxidizing but pro-metabolic agents such as aspirin, thyroid and progesterone would also function as indirect cortisol\/estrogen antagonists because they all result in increased metabolism, which results in a more oxidized state (lower NADH\/NAD+ ratio) and a decrease in the amount of SH groups. There is already plenty of evidence for the anti-cortisol and anti-estrogenic effects of progesterone directly at the receptor level, while the evidence for aspirin is also strong, but medicine has so far failed to explain the mechanism behind aspirin’s endocrine effects. Conversely, accumulation of intact SH groups such as seen in virtually all chronic conditions or as a result of supplementation with SH donors such as GSH, N-acetyl-cysteine (NAC), methionine, cysteine, etc would be expected to promote both cortisol and estrogen signalling. This strongly suggests that supplementing with reducing agents such as GSH, NAC, cysteine, methionine, etc would not be beneficial in healthy people and can be quite dangerous in people with compromised health. I did a post just a few days ago on a study that found GSH to be a key driver of cancer growth<\/a>, by enabling the survival and growth of cells under a state of hypoxia (a key characteristic of cancer and other chronic diseases). Estrogen excess is both a key driver of hypoxia and a result of it, which once again confirms the key role metabolism plays in endocrine disturbances that have mystified medicine for decades and are thought to this day to not be related to metabolism.<\/p>\n https:\/\/pubmed.ncbi.nlm.nih.gov\/7336464\/<\/a><\/p>\n https:\/\/www.jstor.org\/stable\/58687<\/a><\/p>\n