Clin Neuropharmacol. 2007 Mar-Apr;30(2):101-6.
Acute levodopa intake and associated cortisol decrease in patients with Parkinson disease.

Müller T, Muhlack S.

Department of Neurology, St Josef Hospital, Ruhr University Bochum, Germany. [email protected]

Levodopa application improves motor symptoms in patients with Parkinson disease (PD). Levodopa induces lower cortisol plasma levels and decreases serotonergic activity in certain brain areas of fish. The objectives of this study were to perform repeat cortisol concentration measurements before and after the administration of soluble levodopa/benserazide (dose, 200 mg) in 32 patients with PD during an interval of 150 minutes. The cortisol concentrations significantly decreased after levodopa intake, particularly in the patients with more advanced stage of PD, but not in the less affected patients. There were significantly lower cortisol levels in the patients at the advanced stage of PD compared with those of the earlier patients with PD, particularly at -30, 0, and 90 minutes before/after levodopa application. Significant inverse relations were found between the cortisol levels and the Unified Parkinson Disease Rating Scale total score, particularly at 60 and 90 minutes after levodopa intake. Neurodegeneration occurs in striatal regions and in the brain stem of patients with PD. The 5-HT-containing neuronal terminals of the brain stem hypothetically mediate the cortisol level decrease after levodopa intake because these cells contain an important fraction of amino acid decarboxylase. Therefore, this compartment may be the site of enzymatic conversion of superfluous, exogenous levodopa to dopamine. Consequently, short-term levodopa administration also leads to levodopa uptake in these 5-HT-metabolizing neurons, which interferes with the 5-HT synthesis and may cause a decrease of 5-HT levels. These lower 5-HT levels reduce the hypothalamic function and, via the corticotropin axis, the subsequent peripheral cortisol release. [u]Thus, levodopa-induced cortisol decrease may be related to PD progression.[/u]

PMID: 17414942 [PubMed - indexed for MEDLINE]


I've been learnign about Cortisol since a couple of months, as I'm convinced it may play an important role in PD. Cortisol plays a key role in regulating inflammation, our body's anti-stress response, and the way our body processes glucose (sugar), and I have PD and low (free) cortisol levels. The last sentence of the article above, however, adds a whole new dimension: that taking L-dopa meds might impact cortisol levels in a way that makes PD worse. Given that L-dopa meds are so critical to all of us, this makes me think that cortisol might be even more important that I previously thought.

The challenge is that (even assuming all my hypotheses and assumptions are correct), it's not so obvious to manage cortisol levels. Firstly, at least in my case, the problem doesn't seem that my body is producing too little cortisol. The problem seems to be that it is producing too much of another stuff called transcortin and this transcortin thing keeps lots of cortisol tied up... and so I end up having too little free cortisol because I have too much transcortin. Secondly, it's not obvious what one can do about this. Here's what I found so, far:

1. There are meds that can increase cortisol directly (called cortisone or hydrocortisone). However, these are pretty heavy duty stuff and when you start taking them they impact other stuff on your body plus apparently your body looses it's ability to create cortison on its own ... so once you start taking them it's sort of forever. This doesn't look a great approach to me, especially given that (at least in my case) it's not that I don't have too little cortisol to begin with.

2. High levels of estrogen (female sex hormones - which men also have but in lower quantity) apparently is linked with high levels of transcortin. This leads me to thing that taking stuff to lower estrogen might help (while possibly increasing my masculinity :wink:). I'm not too sure about this one yet, as meds that control estrogen can also have nasty side effects.

3. Licorice seems to be another option, as it is known to increase cortisol too. Nobody seems to know exactly how, but one hypotheses is that it does so by making cortisol bind less to transcortin (which in my case would be convenient). Licorice also seems to have a good reputation in helping out with PD, so I have starting taking a little of it just to try. So far, so good (feel a little more energetic, etc), but hard to say as 1000 other factors could have influenced that too. Also, licorice is known to directly increase blood pressure (which obviously can have nasty consequences - especially if your blood pressure is high to begin with) and, if taken in high doses for more than a couple of weeks, apparently messes up other stuff too.

I asked a doctor (an endocrinologist) how to manage my cortisol/transcortin levels - he told me he dis-advise against taking cortisone but didn't know what else to do. He told me we'd investigate a bit and let me know. So far I haven't heard from him yet. In the mean time, I'm wondering if anyone else know how they are doing in terms of cortisol / transcortin levels and if anyone else has any experience with any meds/approaches that impact cortisol/transcortin (the 3 approaches above or anything else that might work).



P.S.: apparently high estrogen levels in men can lead to bigger-than-average breasts (not sure this explains relative breast sizes in women too :wink:); this means that if you're a men and have breasts on the bigger side, you probably have high transcortin too.
P.P.S.: Eating white mushrooms is apparently a good way to reduce estrogen too.
P.P.P.S.: Turnip, I got myself licorice root both in natural form and in pills - the pills ones only taste plastic
i hate mushrooms more than licorice - i'm doomed. and as for cleavage - no comment!
seeemingly shampooos have estrogen! why on earth...i'm coming over all victor meldrew.

Unfortunately, I don't know if one can find mushrooms in pills :wink:

... but no worries! there's also a bunch of other foods that apparently contain substances that are supposed to reduce estrogen production in our bodies (just google aromatase inhibitors). From what I could find so far, they include: red grapes and red wine (contain resveratrol), cocoa, peach, and vineger (contain catechin, and cocoa is apparently also a MAO-B - like Azilect), and parsley, celery, and chamomile tea (rich in chalcones). Nicotine and high zinc foods such as red meats, especially beef, lamb and liver also seem to be reduce estrogens, though they have other problems - as do oysters and lobster (though I haven't checked if they have drawbacks so I can continue to eat them with a clean conscience :grin:)

Also I'm not sure, but soy-based stuff seem to contain lots of phytoestrogens, which apparently limit estrogen when you have too much of it...

Bon appetit,


How much licorice would you suggest having?

Thanks. Samdog
Hi samdog,

Disclaimer: I am not a medical doctor nor otherwise qualified to suggest that people take licorice (or anything else) or do it in certain doses.

Most websites I saw on this topic, recommend that if you wish to take licorice for more than 2 or 3 weeks, then you should not exceed 5 milligrams of licorice per day per kg of body weight (which, for me turns out at around 325 mg per day as I weigh around 65 kg). I believe these doses are for when you actually eat the root (which is the case when you buy pills with tiny bits of root inside). I bought pills containing 450 mg (thus a bit more than the recommended dose for me) and am starting to take 1 of those a day during weekdays. I also bought a package with lots of small root cuts and use these sometimes to make tea. I measured it once and I used around 1 gram of licorice root cuts for 1 cup of team. I’m not sure, but I suspect that when you use licorice root to make tea, you probably get a lower dose of the active ingredients than if you actually take a pill (in the tea, I only let it infuse for 1 minute or perhaps even less).

In terms of when to take the pills, I read somewhere that it is best with meals. I personally have started to take my pill at lunch time.

Note that licorice can have bad consequences too. I found the following warning about it: “Pregnant women shouldn't take licorice supplements because it may increase preterm labor risk. If you have heart, liver or kidney problems, diabetes, high blood pressure or problems with fluid retention you should also avoid taking these supplements. Licorice can interact with certain medications, including diuretics, ACE inhibitors, corticosteroids, laxatives, diabetes medications, oral contraceptives, MAO inhibitors, steroids, blood pressure medications, hormone therapy and digoxin”. Also note that Azilect (rasagiline) is a MAO inhibitor (and I, like many of us, am taking it). Finaly, also note that one can find “deglycyrrhizinated licorice” (de-glycyrrhizinated licorice or DGL) which doesn’t seem to have many of the bad side effects of natural licorice. Unfortunately, it’s doesn’t help either to manage cortisol levels, so I personally went for the "natural" licorice.

Hope this helps and brs,

A lot to consider, thank you for your detailed reply

Best wishes

Husband has had low B/P all his adult life but now has PD and life is becoming very difficult, at first very low B/P when standing 53/35 now it lasts all morning and into the afternoon, have just bought Solgars Licorice root extract 225mg per capsule I intend to give him one in the evening before bed and one in the morning when he gets up, when he takes Sinimet 250/25 later in the morning he takes Rasagilina 1mg with no perceived improvement also an Ebixa patch and Memantina.
He has also been prescribed Imiquimidod for a skin condition which I know can have nasty side effects, does any one have any idea on how all these medications work with each other and has the Licorice root extract helped anyone.

We are a bit isolated here as we live in rural Spain and can not pop in to see a parkinson's nurse.