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Glucose Is Anabolic For Thymus, Opposes Catabolic Effects Of Cortisol

haidut

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As most of my readers know, cortisol is a highly catabolic steroid and one of the main agents (estrogen being another) responsible for thymus atrophy with age. These catabolic effects of cortisol can be blocked by progesterone, DHEA, pregnenolone, and even DHT (but not by testosterone). The study below confirms the catabolic effects of cortisol on thymus, and its ability to lower ATP levels. It also demonstrates that we can now add dietary factors to the list of agents that affect thymus size/atrophy and as such may oppose the catabolic effects of cortisol on thymus. The study examined the effects of a number of sugars as well as their metabolites pyruvate and lactate on thymus growth, and discovered that glucose was by far the most potent stimulator of thymus anabolism. The study suggests that these effects of glucose were likely due to the ability of glucose to increase synthesis of adenine nucleotides (including ATP) and of the intermediate glucose-6-phosphate. Btw, inosine is one of the adenine nucleotides and, in corroboration of the claims of the study below, it is worth noting that inosine has a known potent immunostimulant effect and is in fact approved as an anti-viral drug (Inosine Pranobex / Isoprinosine) in many European countries. In further corroboration of the study below, inosine is known to elevate ATP levels through a nucleotide salvaging pathway. It would have been really interesting for the study to also test the effects of fatty acids on thymus growth, but I suppose for now we just have to accept the consolation prize that glucose is highly beneficial for the immune system and won't make you vulnerable to infectious disease, as many doctors claim.

http://www.jbc.org/content/244/8/2210.full.pdf

"...Amino acid incorporation into thymus cell protein is at least partly dependent upon glucose metabolism or, perhaps stated more accurately, dependent upon metabolites derived from glucose. We have not yet found a combination of substrates at any concentration which can completely replace glucose, whereas even small concentrations of glucose (Fig. 2) maintain incorporation at higher levels than are obtained with large concentrations of readily metabolized substrates such as pyruvate and lactate. It seems reasonable to tentatively attribute the special effects of glucose to its ability to provide glycolytic intermediates at the level of glucose-6-P. Our findings that, when compared with low levels of glucose, lactate and pyruvate also slightly elevate glucose-6-P, and that under these conditions equal rates of amino acid incorporation are associated with equal levels of glucose6-P, raise the possibility that the effects of pyruvate and lactate on incorporation may also be at least partly through their ability to provide, or spare, glycolytic intermediates."

"...In these studies of rates of amino acid incorporation we have shown that the stimulatory effects of carbohydrates are associated with substantial increases in ATP levels, and that the inhibitory effects of cortisol are associated with, and usually preceded by, smaller but distinct inhibitions of the ability of glucose and other carbohydrates to produce ATP. The observed ATP changes are usually associated with reciprocal changes in ADP and AMP. These data suggest a working hypothesis to be tested by further experimentation that the effects of substrate and of cortisol are in fact mediated through changes in adenine nucleotide levels, which in turn influence amino acid incorporation rates."

"...Cortisol addition leads to an early inhibition of only the carbohydrate-dependent amino acid incorporation into protein. This hormone effect is associated with a cortisol inhibition of the ability of glucose and other carbohydrates to generate ATP, the effects on ATP in some instances preceding the effects on incorporation. With glucose as substrate, effects of cortisol on ammo acid incorporation may be attributed to a prior inhibition of glucose uptake; with lactate and pyruvate as substrate, effects on substrate uptake and on the initial metabolic steps were not found. Although the inhibition of glucose uptake is not the unique action of cortisol, the results suggest that hormonal inhibition at this site has considerable physiological significance. "
 

tankasnowgod

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Jan 25, 2014
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Another thread about thymus anabolism with no comments. Weird.

Guess no one is interested in increasing their immunity. Must be due to all those news outlets talking about how not a single person in the world is sick right now, certainly not with a bizarre virus that they claim came from a bat or whatnot.
 

LucyL

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Oct 21, 2013
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Thymus extract has suddenly been discovered as the "cure for COVID and cancer" (When No One Was Looking, Dietary Supplements Cured Cancer & Covid-19 - LewRockwell LewRockwell.com)
From Bill Sardi's article:
In an astounding study the public has not heard about, the subcutaneous (under the skin) injection of just 1.6 milligrams of a thymus gland hormone (thymosin alpha-1) for seven days among patients with severe deathbed COVID-19 coronavirus disease dramatically increases T-cell counts and slashes the mortality rate by 272% (from 30% to 11%) without side effects.

He posits zinc as a substitute for thymosin alpha-1, with no mention of glucose though.
Zinc deficiency not only results in the involution (shrinkage) of the thymus gland from the size of a walnut to the size of a pea with advancing age, and impairs the ability of the thymus gland to produce peptide (amino acid) hormones such as thymosin-A1.
 

yerrag

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Another thread about thymus anabolism with no comments. Weird.

Guess no one is interested in increasing their immunity. Must be due to all those news outlets talking about how not a single person in the world is sick right now, certainly not with a bizarre virus that they claim came from a bat or whatnot.
If you've been around RPF long enough, you'd already know that Ray Peat has said that cortisol destroys the thymus gland, and the thymus gland is where T-cells mature. Too much cortisol results in too little T-cells being produced, and this affects greatly in lowering our immunity.
 

Ben.

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A antidepressant rebuilds the thymus glands that have been damaged by stress? Interesting ....

It does not sound good on the serotonin front, and i woudln't want to take antidepressants ever ... but just as with any medications, these substances do more than just whats advertised on the package ...

The mechanisms of imipramine's actions include, but are not limited to, effects on:

  • Serotonin: very strong reuptake inhibition.
  • Norepinephrine: strong reuptake inhibition. Desipramine has more affinity to norepinephrine transporter than imipramine.
  • Dopamine: imipramine blocks D2 receptors.[30] Imipramine, and its metabolite desipramine, have no appreciable affinity for the dopamine transporter (Ki = 8,500 and >10,000 nM, respectively).[31]
  • Acetylcholine: imipramine is an anticholinergic, specifically an antagonist of the muscarinic acetylcholine receptors. Thus, it is prescribed with caution to the elderly and with extreme caution to those with psychosis, as the general brain activity enhancement in combination with the "dementing" effects of anticholinergics increases the potential of imipramine to cause hallucinations, confusion and delirium in this population.
  • Epinephrine: imipramine antagonizes adrenergic receptors, thus sometimes causing orthostatic hypotension.
  • Sigma receptor: activity on sigma receptors is present, but it is very weak (Ki = 520 nM) and it is about half that of amitriptyline (Ki = 300 nM).[citation needed]
  • Histamine: imipramine is an antagonist of the histamine H1 receptors.
  • BDNF: BDNF is implicated in neurogenesis in the hippocampus, and studies suggest that depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis. It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in murine models do not show anxiety related or depression related behaviours. Chronic imipramine administration results in increased histone acetylation (which is associated with transcriptional activation and decondensed chromatin) at the hippocampal BDNF promoter, and also reduced expression of hippocampal HDAC5.[32][33]
 

Inabruzzo

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Joined
Dec 28, 2020
Messages
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Thymus extract has suddenly been discovered as the "cure for COVID and cancer" (When No One Was Looking, Dietary Supplements Cured Cancer & Covid-19 - LewRockwell LewRockwell.com)
From Bill Sardi's article:
In an astounding study the public has not heard about, the subcutaneous (under the skin) injection of just 1.6 milligrams of a thymus gland hormone (thymosin alpha-1) for seven days among patients with severe deathbed COVID-19 coronavirus disease dramatically increases T-cell counts and slashes the mortality rate by 272% (from 30% to 11%) without side effects.

He posits zinc as a substitute for thymosin alpha-1, with no mention of glucose though.
Zinc deficiency not only results in the involution (shrinkage) of the thymus gland from the size of a walnut to the size of a pea with advancing age, and impairs the ability of the thymus gland to produce peptide (amino acid) hormones such as thymosin-A1.
Great information @LucyL. We’re picking up some Thymus supplement for the house for our son soon to be at school in case there is any covid issues.
 
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