Milk Thistle (silibinin) May Treat Cushing Disease And High Cortisol

[Bart1]

@haidut sorry to tag you again but you are sort of the expert on cortisol

If one would get a cortisol test. How long before the test does one need to quit supplements like progesterone and anti-histamines? I’m asking because I assume they interfere with the test? Also you mention in a podcast with Danny to do a an am and pm bloodtest, however I see in my country they probably do an 24 hour urine test, is that equally effective in detecting abnormalities? Thanks for your time.

 

[Wilfrid]

Maybe it can mess with TH ( especially T3 ) as well: Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8. - PubMed - NCBI

 

[success23]

Can you have Cushing but not feel very stressed?

 

[Michael Mohn]

This is AWESOME! Do you mind sharing what brand you are taking and where you get it from? I really hope I can get him to stick with it. Right now we are using a German pharmaceutical. Thank you!

Can you say what German brand you used? Thank you for your answer.

 

[success23]

Maybe it will be best to stack the milk thistle extract with some piperine and lower the dosage. It will be most cost effective.

 

[IROM]

An ingredient in Rockstar Energy drink (exclusively I think) it is the reason my body only craves Rockstar and not other energy drinks because I don't get all the stress cortisol induced effects from chugging caffeine, preservatives and overly concentrated supplements. If Rockstar was dilluted it would probably be Peaty.

 

[Barbarossa]

I don't have access to the study but it was both in vitro and vivo. The group behind the research has already filed a patent on silibinin for treating Cushing disease, so they sure believe it is effective. Give the suppression of silibinin on ACTH, this probably led to significant reductions in cortisol as well since symptoms in the treated mice disappeared completely. Milk thistle may be another option for reducing cortisol, even though it is estrogenic in higher doses. It also chelates iron, which explains some its protective effects on the liver and neurodegenerative diseases like Alzheimers.

http://planetsave.com/2015/02/17/milk-t ... rch-finds/
http://www.nature.com/nm/journal/vaop/n ... .3776.html

HAIDUT what is the highest dosage against Cushing Disease (pit tumor) ? i know human equivalent dosage is 1000-1500 mg is good, but can I take higher dosage? I can feel some relief with milk thistle with 1500mg

I have some low cortisol symptoms like nausea and no hunger

 

[cs3000]

Maybe it can mess with TH ( especially T3 ) as well: Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8. - PubMed - NCBI

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8

Abstract. Thyroid hormones (THs) are charged and iodinated amino acid derivatives that need to pass the cell membrane facilitated by thyroid hormone transmembra

academic.oup.com

ty , same mechanism with Emodin (Cascara) which inhibits MCT8 thyroid transporter , a little more potently even than silychristin
https://www.researchgate.net/public..._Thyroid_hormone_transporter_MCT8_as_a_target emodin
In particular, compound emodin displayed the most potent activity against MCT8 with a binding energy value of −8.6 kcal/mol silychristin (−8.2 kcal/mol)

The most specific transporters identified so far are OATP1C1 and MCT8, which appear to be involved in T4 transport across the blood-brain barrier, and in T3 transport into brain neurons, respectively.. mutations in MCT8 are associated with X-linked severe psychomotor retardation and elevated serum T3 levels
^ defective mct8 elevates t3 in serum because less is being taken in by cells ,
which tells us things that raise T3 levels are not always good by default , as could indicate less cellular intake

Indeed, comprehensive pharmacokinetic studies measuring the plasma concentrations of SY compounds in three healthy volunteers underline a possible physiological impact of SC. After a single oral administration of 600 mg milk thistle extract, SC reached a peak plasma concentration (after 1–3 h) of 53.8 ng/mL. This is equal to approximately 110 nM and in the range of our in vitro IC50 values (29). Because TKIs have significant effects on the TH axis with plasma levels, even 1 order of magnitude below their IC50 (7), an in vivo effect of SC is even more likely.

Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract

Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle ( Silybum marianum ), is composed mainly of silychristin, silydianin, silybin A, silybin B (SBB), isosilybin A (ISBA), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated...

dmd.aspetjournals.org

half life of silychristin is 1 - 3 hours , or 3-8 hours if the conjugated form in the body has the same effect. so inhibition would last a while depending on concentration needed

the other main compounds in silymarin are way less potent in the micromole range instead of nanomole (so 60x - 100x less potent than silychristin). so silychristin % in milk thistle extract is solely responsible

question is what concentration in blood needs to be maintained to keep the inhibitory effect lasting?
they said in humans peak plasma concentration of SC = 53.8ng/ml = equivalent to 110nM in vitro. which inhibits thyroid transporter 50%.

https://dmd.aspetjournals.org/content/dmd/36/1/65/F5.large.jpg

^ by that 600 mg of standardized milk thistle extract in humans , keeps the concentration ~20ng/ml - 40ng/ml for ~8 hours


The good news is MCT8 doesn't only effect thyroid transporter into the cell. also out from cells.

MCT8 facilitates not only the influx but also the efflux of its substrates (23). To examine the SC effect on the export mechanism of MCT8, we first loaded the cells with [125I]-T3 for 45 minutes and measured the T3 release after 3 minutes with or without the presence of 1 μM SC. SC significantly reduced the efflux of T3 by 68% after 3 minutes (Figure 3).

So while it stopped T3 getting into cells it also reduced T3 release from cells by 68%.
So theres a balancing effect

The relative T3 uptake (5 μM f.c.) ± SC (5 μM f.c.) by MCT8-MDCK1 was measured over time. In the presence of SC, the relative T3 uptake was reduced by approximately 70%–80%

actually it might even be a net benefit to keeping more T3 in cells , unless the effect saturates at lower dose
as they used 5μM dose to inhibit T3 intake 70%-80%, but only 1μM dose to stop 68% t3 leaving cells

 

[cs3000]

the other main compounds in silymarin are way less potent in the micromole range instead of nanomole (so 60x - 100x less potent than silychristin). so silychristin % in milk thistle extract is solely responsible

question is what concentration in blood needs to be maintained to keep the inhibitory effect lasting?
they said in humans peak plasma concentration of SC = 53.8ng/ml = equivalent to 110nM in vitro. which inhibits thyroid transporter 50%.

https://dmd.aspetjournals.org/content/dmd/36/1/65/F5.large.jpg

^ by that 600 mg of standardized milk thistle extract in humans , keeps the concentration ~20ng/ml - 40ng/ml for ~8 hours


The good news is MCT8 doesn't only effect thyroid transporter into the cell. also out from cells.

So while it stopped T3 getting into cells it also reduced T3 release from cells by 68%.
So theres a balancing effect

actually it might even be a net benefit to keeping more T3 in cells , unless the effect saturates at lower dose
as they used 5μM dose to inhibit T3 intake 70%-80%, but only 1μM dose to stop 68% t3 leaving cells

update to that i tried it for a while around that time , cant be 100% sure it was just that because calorie intake has been all over the place.
but i definitely noticed colder temps around that time. didnt measure back then but by feeling temp was dropping a lot at times. so i think the net effect is thyroid inhibition. didnt have a lasting effect for intestine purposes either way. and stopped because of effect on energy (lowering iron probably)

 

[Michael Mohn]

Have him on the Nootropics milk thistle. He has good days and bad days. I would love the Cushings to disappear overnight as it sucks so much. I will say, his liver enzymes are back in the normal range. Now he has high white blood count but the liver is better. Still has crushing depression, though.

Hi, is there an update on your son's health?