Elevated cortisol/DHEA-S ratio (a sign of chronic stress or low metabolism) may drive Alzheimer Disease (AD)
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As my readers know, from both Ray work and mine, cortisol has a proven detrimental role in virtually all organs/tissues when chronically elevated. As misguided as mainstream medicine is, it has already admitted the role of cortisol in a variety of mental health conditions including depression, anxiety, bipolar disorder, schizophrenia, etc. However, arguments are still being made that cortisol’s role is not completely “clear” since many studies have failed to find consistently elevated cortisol levels in mental disorder patients. As I have stated numerous times on various podcasts and blog posts, this “discrepancy” is likely due to fact that serum cortisol levels vary significantly throughout the day and can change in a matter of seconds. As such, single or infrequent measurements often fail to capture the chronic trends for cortisol levels, and most studies rely on just a single such measurement in serum. In addition, as many studies (and my research group’s own experiments) have shown, it is the absolute levels of cortisol that matter, but rather the ratio of cortisol to one or more of the anti-glucocorticoid steroids our bodies produce. Namely, multiple studies have demonstrated that the ratio of cortisol/DHEA-S, cortisol/DHEA, cortisol/testosterone, cortisol/progesterone, etc are much more predictive of existing or future pathologies since those ratios demonstrate whether cortisol’s known negative systemic effects are counterbalance (or not) by at least one of those cortisol antagonist steroids. Case in point, multiple studies have demonstrated that the cortisol/DHEA-S or the cortisol/DHEA ratio is the single most reliable predictor of all-cause mortality as well as any future morbidity, even when measured in serum where cortisol levels fluctuate greatly and are often unreliable as single-point measurements. If cortisol and one or more of the anti-cortisol steroids are instead measured in hair or nails, the predictive power of the ratio increases dramatically as it truly represents long term trends in both cortisol levels as well as one or more of its antagonists.
In any event, the study below demonstrates (I think, for the first time) that the cortisol/DHEA-S ratio is elevated in patients with AD and this elevation likely plays a causal role in the pathology of AD. As such, lowering that ratio by lowering cortisol levels, increasing DHEA(S) levels, or both should be highly therapeutic. Aspirin, pregnenolone, progesterone, emodin, thyroid, niacinamide, glycine/gelatin, etc are some of the well-known remedies for elevated cortisol, and taking DHEA can itself both lower cortisol (DHEA is an inhibitor of 11b-HSD1 and activator of 11b-HSD2) and raise DHEA(S) levels. A combination of two or more of these remedies will likely have a synergistic effects on the cortisol/DHEA-S ratio and this may alleviate AD. Finally, the study undescores the dangers of chronic stress and/or hypothyroidism as those are the primary factors in raising cortisol, lowering DHEA(S), and thus raising the cortisol/DHEA-S ratio.
“…No statistically significant difference in serum DHEA-S concentrations was found between patients with AD and controls. However, patients with AD had significantly higher cortisol levels (398.85 vs. 337.40 nmol/L; p = 0.026) and a higher cortisol/DHEA-S ratio, showing a trend toward statistical significance (p = 0.078). Among participants aged 65-75 years, the cortisol/DHEA-S ratio was significantly higher in patients with AD than in controls (p = 0.031). In the control group, males had significantly higher DHEA-S levels than females (p = 0.020), whereas no sex difference was observed in the AD group. The findings of this pilot study suggest that elevated cortisol levels and an imbalance in the cortisol/DHEA-S ratio may contribute to AD pathophysiology. DHEA-S alone did not show a significant association with disease presence, but the observed age- and sex-related differences indicate that this neurosteroid may play a differential role in the development and progression of AD.”