Licorice and its pharmacology

[Journeyman]

In spite of following a fairly judicious methylation protocol and healthy diet since mid 2013 (3.5 years now) I find that I'm both easily stressed out and positively exhausted after a morning gym session, from which I only feel close to normal the next day.

Suspicious of adrenal fatigue following low morning and day salivary cortisol levels going back as far as 2005 (When I was 24 btw) I've revisited the options to support adrenal fatigue from an adaptogenic herbal perspective. This invariably led me to this https://examine.com/supplements/licorice/
however I've some reservations about whether licorice would be a good adrenal support for me given its primary focus on raising cortisol, which according to my blood type (A) might not be a good thing since apparently I'm already pre-disposed to elevated cortisol levels in response to fairly minimal stressors, and have a tendency to clear it slowly once its created... and without diverting too much from the primary purpose of this post I would say that I'm in complete confusion over whether I have too high or too low Cortisol levels. Firstly I do tend to be anxious and vulnerable to relatively minor stressors (associated with elevated Cortisol levels) with fairly high blood sugar levels, but on the other hand I don't have middle body obesity (indeed I'm 10% body fat) and my salivary cortisol results from my 'prime' suggested I had too low Cortisol levels... (though this was on a day where I had no stressors whatsoever so perhaps if it was a normal work day it would have been totally different)... Go figure..

Now according to the same linked article above, if I had any concerns about the Testosterone lowering / Cortisol raising effects of Licorice I can opt for Deglycyrrizinated (DGL) Licorice where the Glycyrhizzin has been removed with some additional side benefits such as less risk of lowered Potassium (hypokalemia) and high BP (neither of which would concern me since I tend towards Low BP and have ample Potassium supplementation)

However before choosing DGL or normal Licorice I really think its worth understanding what benefits I'm missing out on noting that the previously linked article seems to suggest that its the Glyzzhirizzin component that is responsible for promoting Cortisol levels and thus (presumably) giving the adrenal support function that Licorice is known for?? Are there other saponins or components that give adrenal support in licorice? and if so what kind of significance are they or is it primarily the Glyzzhirizzin that gives the adrenal support?

Will I effectively be throwing the baby out with the bath water by getting licorice without the Glycyrhizzin content??

 

[LINE]

Here is a good link about the use of licorice in TCM (Traditional Chinese Medicine) and they emphasize there is a difference between TCM licorice and other varieties. They state there are other plant chemicals besides glycyrhizzin.
http://www.herbslist.net/chinese-licorice-root.html

herbs2000.com has great info on herbs http://www.herbs2000.com/herbs/herbs_licorice.htm

My experience with the whole licorice was not favorable. I took it and it definately accelerated my metabolism, my adrenals were already cooked and I could tell it pushed the adrenals. I started sweating, had increased anxiety. It was not a good thing. I also tried the DGL in which I did not notice any benefit.

My favorites are adaptogenic (tonifying) herbs such as turmeric. I think it (turmeric) is beneficial on a number of levels, it is anti inflammatory, antibiotic, protects the heart, protects the liver and protects the neurological system. According to many, you have to dose bigger shots or use it in warm water since it is hard to assimilate.

I also use ashwaganda which is another adaptogen that seems to help.. http://www.herbs2000.com/herbs/herbs_ashwaganda.htm, I have also used Siberian Ginseng, Jiaogulan and Moringa, all three of these seemed beneficial. At this point I stay on turmeric, ashwaganda and ceylon cinnamon all purchased in bulk and organic.

Magnesium is probably one of the most important supplements for me since it is involved in so many metabolic processes. Magnesium is vital to adrenal function as well as neurological health, the immune system, production of glutathione and so much more. Magnesium is lost under any type of stress (physical, emotional, mental and biological stress). Doctors Best High Absorption has been a great form, it contains mag lysinate and glycinate which are both very bio available.

 

[Journeyman]

Thats a truly excellent article there which finally goes a bit deeper than the numerous copy/paste jobs out there that simply read 'licorice supports the adrenals' or 'licorice heals the adrenals' with no further explanation as to the mechanism of action.

Having said that I'm not sure its clear whether its the glycyrrizhin component that is responsible for reducing the conversion of cortisol to cortisone which seems to be the main mechanism by which licorice 'increases' cortisol.

I also note that earlier in the article it explains that licorice anti inflammatory property comes from the fact that it mimics a corticosterone
i.e.:

"Licorice has an anti-inflammatory, antiallergic and antiarthritic effect similar to that of cortisone but without its side effects. This is because of glycyrrhizin which has a structure similar to hormones produced by the adrenal glands."

So in putting this together with the other section:

"Licorice has the ability to prolong and increase the action of the steroid hormone cortisol produced by the adrenal glands. It does this by slowing down the conversion of cortisol into cortisone."

Is it accurate to surmise that licorice doesn't actually increase cortisol levels, but rather increases the half life of cortisol produced, and adds the equivalent of corticosterone which further reduces the tendency for existing cortisol to get used up in any necessary conversion from cortisol to corticosterone?

I look forward to your insights/thoughts

Journeyman

 

[Journeyman]

Thats a truly excellent article there which finally goes a bit deeper than the numerous copy/paste jobs out there that simply read 'licorice supports the adrenals' or 'licorice heals the adrenals' with no further explanation as to the mechanism of action.

Having said that I'm not sure its clear whether its the glycyrrizhin component that is responsible for reducing the conversion of cortisol to cortisone which seems to be the main mechanism by which licorice 'increases' cortisol.

I also note that earlier in the article it explains that licorice anti inflammatory property comes from the fact that it mimics a corticosterone
i.e.:

"Licorice has an anti-inflammatory, antiallergic and antiarthritic effect similar to that of cortisone but without its side effects. This is because of glycyrrhizin which has a structure similar to hormones produced by the adrenal glands."

So in putting this together with the other section:

"Licorice has the ability to prolong and increase the action of the steroid hormone cortisol produced by the adrenal glands. It does this by slowing down the conversion of cortisol into cortisone."

Is it accurate to surmise that licorice doesn't actually increase cortisol levels, but rather increases the half life of cortisol produced, and adds the equivalent of corticosterone which further reduces the tendency for existing cortisol to get used up in any necessary conversion from cortisol to corticosterone?

I look forward to your insights/thoughts

Journeyman

I think I figured out a part of the puzzle here after researching the difference between cortisol and cortisone which then prompted me to do a google search for '11 b-HSD and licorice' to identify if it was this enzyme that licorice was influencing... which indeed it seems it was: https://en.wikipedia.org/wiki/11β-Hydroxysteroid_dehydrogenase

and it also seems to confirm that its the glyzyrrizin component that does the main if not sole job. It seems that by posing as cortisone licorice (particularly glyzyrrizin) causes the body to downregulate its 11 B-HSD activity so as to keep cortisol as cortisol rather than having it convert to cortisone as it tends to when 11 B-HSD is elevated.

Sound accurate? Anything additional?

 

[LINE]

You did a great job researching this and finding the answer - well done. You helped me fill in some of the missing links on this.

One thing that comes to mind is the role of the adrenals in health and the two concepts of adrenal activity. In adrenal activity there can be 2 versions, the first is low output while the other is higher output. Some think that high viral loads slow the metabolic rate down and causes a low adrenal output. In this case perhaps the licorice would be helpful.

It makes sense that the Chinese regard licorice as a favored herb since it would help produce the hormones that bring healing much like cortisone is considered a miracle drug. My suspicion is that the Chinese would not put a patient on licorice for long periods of time but rather a shorter period of time to remedy an acute illness, just as long term use cortisone is not recommended.

The other side of the coin is the high adrenal output which is linked to humoral immunity or a Th2 immune response. Humoral immunity usually involves T cells and other immune cells which are provoked during certain types of infections. This immune reaction raises the HPA axis thus stimulating the adrenals to output hormones as part of the defensive measure.

In my case, I went into adrenal overdrive due to a Th2 immune event and developed excessive adrenal output (Cushings- like or hyperadrenalism). This situation will burn the adrenals out pretty quickly and if the adrenals are not restored then you crash. Most stimulants work by provoking the adrenal response, so any stimulation would send me deeper in the hole this is why licorice sent me into hyper metabolic meltdown.

Since the adrenals are capable of producing adequate hormones, I have found it beneficial to nutritionally support them and use the tonifying adaptogenic herbs as mentioned above. Here is my article on adrenal fatigue http://patrickrambling-pb.blogspot.com/2012/02/adrenal-fatigue.html

I would appreciate your feedback.