Mucuna + carbidopa = vomiting? What's going on? Help please!

[1LittleWillow]

As I've mentioned elsewhere, I normally take Barlowe's Brown Indian Mucuna instead of Sinemet (VERY bad reaction to Sinemet which got worse over time when I tried it for a few months in early 2021). The Barlowe's capsules are 650 mg extract with 40% L-Dopa, so approximately 260 mg L-Dopa each. I take them on an as-needed basis, and I don't take any Rx'd meds at all.

When I take the Barlowe's caps by themselves with a little green tea, I have to take 3 at a time, they take 2 hours to kick in, and I only get 2-3 hours of symptom relief. Because my symptoms aren't severe yet, this has been acceptable to me up to this point. I don't use very much per week as my symptoms without it are generally tolerable, and on most days I don't take anything at all.

HOWEVER... we're going on a 7-day vacation soon and I'd like to feel "normal," so I've been experimenting to see if there's a way to take less mucuna and get a longer "on" time. My MDS prescribed carbidopa 25mg tabs to try. If I take 1 Barlowe's capsule with 1/4 tab carbidopa (6.25 mg), it kicks in within about 30 minutes, and lasts about 5 hours, which is awesome, but I consistently have about 15 minutes of significant nausea/vomiting beginning around the 30-minute mark.

I can't talk to my MDS about this again until after the vacation, so I'm hoping someone here might have some insight into why adding the carbidopa would make me vomit when taking mucuna alone doesn't. I LOVE the fact that it kicks in so quickly and predictably with the carbidopa, and of course the long "on" times are fantastic, but I don't know if I can manage the vomiting while we're on vacation.

Is it because the addition of carbidopa makes it too effective, so I need a smaller dose of mucuna? I'm so confused lol. I thought the whole point of carbidopa was to PREVENT vomiting by getting the levadopa/L-Dopa into the brain by preventing peripheral metabolism.

FYI, when I was trying Sinemet (Jan. 2021), I was vomiting constantly, so my MDS tried adding additional carbidopa (25 mg) to each dose. It didn't help with the vomiting at all. Also, I've never experienced dyskinesia with any of the drugs/dosages/combinations I've tried.

I asked this same question about a year ago but never got any replies that helped me figure it out, so I just gave up on the carbidopa, but I'd really like to find a way to make this work. Thanks!

[chartist]

Vomiting is a known side effect of Sinemet :

drugs.com/sinemet.html#side...

Art

[park_bear]

Let us see what we can figure out here. Your case is atypical so we can take nothing for granted. As you know, the purpose of carbidopa is to prevent levodopa from being turned into dopamine in the gut, which usually causes nausea, and also prevents it from getting into the brain because dopamine cannot cross the blood brain barrier. The fact that carbidopa makes your Mucuna so much more effective tells us a few things:

1. That without the carbidopa, much of the levodopa in the Mucuna is being turned into to dopamine

2. The carbidopa is preventing this

3. That the dopamine (that occurs without the carbidopa) is not making you nauseous

So the possibility arises that it is the carbidopa that is causing you nausea. You can test this possibility by taking some carbidopa without the Mucuna.

[1LittleWillow in reply to park_bear]

Makes sense! It seems like 6.25 mg is such a tiny amount, but I do have weird reactions to a lot of other drugs, so it's certainly possible. I'll try the carbidopa alone and post my results.

[WinnieThePoo in reply to 1LittleWillow]

not really. It's much more likely that the nausea is caused by the carbidopa allowing more dopamine to be made in the brain (which it is supposed to do) and you reacting to higher dopamine levels. Some people are just more prone to this than others.

The fourth ventricle of the brain hosts the vomiting centre. The floor of the fourth ventricle contains an area called the chemoreceptor trigger zone (CTZ). It is also called the area postrema. When the CTZ is stimulated, vomiting may occur.

The CTZ contains receptors for dopamine, serotonin, opioids, acetylcholine and the neurotransmitter substance P. When stimulated, each of these receptors gives rise to pathways leading to vomiting and nausea

[Gioc in reply to WinnieThePoo]

WTP,

Part of what you write is copy and paste of this article on vomiting and its correlation with dopamine and other conditions due to PD. I think it is interesting in its entirety.

I quote:

news-medical.net/amp/health...

[WinnieThePoo in reply to Gioc]

or this

en.m.wikipedia.org/wiki/Che...

Or, a bit cheeky since it's copyright this from the reference textbook by Eric ahlskogs

More to the Story: Carbidopa

Nausea and vomiting was a limiting factor for some PD patients during the early years of levodopa therapy in the early 1970s. Although this nausea is not associated with damage to the stomach (it does not cause ulcers or injure the stomach lining), it often prevented adequate dosage. As we discussed earlier, nausea is caused by premature conversion of levodopa to dopamine outside the brain. Once dopamine is generated within the circulation, it is unable to cross the blood-brain barrier, but it does pass into the brainstem nausea center (the chemoreceptive trigger zone). Cleaver scientists quickly recognized how to block this premature conversion of levodopa to dopamine outside the brain. The solution was the creation of a substance that would block the conversion of levodopa to dopamine in the circulation but not in the brain.

[HekateMoon in reply to 1LittleWillow]

i wonder if bensezaride wich is the carbidopa equivalent in madopar, would have the same effect.

[WinnieThePoo in reply to park_bear]

I know this is going to fall on stoney ground but the purpose of carbidopa is NOT to prevent levadopa being converted to dopamine in the gut. It is absorbed into the bloodstream and inhibits conversion of levadopa in the general metabolism outside the blood brain barrier. A significant proportion of that activity is in the gut wall, but the activity occurs in the nerves of the gut, and not in the gut itself. Nausea is not exclusively a function of the gut. Think car sick, or sea sick (and other motion sickness). Think of retching at the smell in the dogs room after a night of diahorrea, or when eating something that triggers it (tomatoes in my case as a kid). And any number of neurological conditions which cause nausea. Think CTZ

[park_bear in reply to WinnieThePoo]

I have already refuted your contention on this issue. The stony ground is all yours:

The motivation for the development of Sinemet - which is a contraction of "sin emesis" - without nausea - was to prevent nausea induced by conversion of levodopa to dopamine in the gut by DDCs.

frontiersin.org/articles/10...

"When levodopa is administered orally, it is absorbed in the proximal small intestine, where it has to be actively transported from the lumen over the intestinal epithelial barrier into the blood stream. To prevent peripheral and intestinal levodopa metabolism by DOPA decarboxylase (DDC), peripheral DDC inhibitors, such as carbidopa, are co-administered with levodopa. "

movementdisorders.onlinelib...

"When l-dopa is given orally, there is almost complete absorption of the drug, and only 2% is eliminated unmodified in the feces; however, only approximately 30% of an oral dose of l-dopa, given alone, reaches the systemic circulation intact. Because of an extensive first-pass metabolism and rapid plasma clearing by decarboxylation to DA at the intestinal level and in the liver, only 1% of an oral dose of l-dopa enters the brain unmodified"

Of course it is neurons in the gut that are involved in the nausea. So what? It is still occurring in the gut, which is what you are attempting to disagree with.

The other neurological conditions you refer to that also cause nausea are not as a result of excess dopamine in the gut

[WinnieThePoo in reply to park_bear]

just wrong. But never mind

[park_bear in reply to WinnieThePoo]

I cite journal references. You cite your imagination.

[WinnieThePoo in reply to park_bear]

en.wikipedia.org/wiki/Aroma...

No - my Dad worked on this at the launch. Look anywhere - DDCI's operate in the peripheral metabolism , not the gut

[WinnieThePoo in reply to park_bear]

pubmed.ncbi.nlm.nih.gov/270...

The problem with finding you references, is that anyone who knows anything about the subject, knows that the decarboxylation by the enzyme occurs in the bloodstream and not the gut. I might as well try finding you a reference that it doesn't occur in your shoes.

(but although I can't find the reference - it doesn't occur in your shoes!)

[park_bear in reply to WinnieThePoo]

Thanks for providing references. Since we have conflicting references on this matter, going forward I plan on referring to DDCI action in sufficiently general terms to avoid repeating this dispute.

[WinnieThePoo in reply to park_bear]

OK PB. I appreciate your concern for scientific rigour but Dr Google is a fickle source. It may seem it doesn't matter how or where a DDCI like carbidopa works, or where the site of origin for nausea is located . But if you want to treat the nausea, or address the variable response to carbidopa efficacy then it doesn't help to muddle how carbidopa works - which is on enzymatic decarboxylation in the bloodstream,

Levadopa can be converted into wasteful, toxic, nausea inducing dopamine in the gut (that is, the place where poo is made and transited) and that can reduce the amount available to reach the bloodstream where carbidopa can prevent (significantly inhibit) enzymatic decarboxylation. The composition of the microbiome affects this and may explain the variable responses to C/L in PWP.

science.org/doi/10.1126/sci...

news-medical.net/health/Gut...

[pakehamack in reply to park_bear]

Ever since I began viewing this forum, #park_bear has always been a solid voice of reason and a learned responder. If anyone can help you out he can! Of this, I'm certain...

[1LittleWillow in reply to pakehamack]

Agree.

I'm still tweaking and experimenting and having success. I'm going to post again soon when I feel I'm getting consistent results.

[chartist]

Vomiting is also a known side effect of Carbidopa alone :

drugs.com/mtm/carbidopa.htm...

Maybe you can reduce the dose further or try the EGCG route if your liver enzymes are normal.

Art

[1LittleWillow in reply to chartist]

The EGCG (green tea) just doesn't seem to do much at all. It's quite frustrating.

[chartist in reply to 1LittleWillow]

I was thinking of the more potent extract form, not tea. The extract is available into the 90% range.

Art

[1LittleWillow in reply to chartist]

I didn't know that. It didn't even occur to me to check because my MDS added more to help with the vomiting. Oof!

[chartist in reply to 1LittleWillow]

Maybe halving the current dose further may be useful.

Art

[WinnieThePoo in reply to chartist]

I think you are mistaken. The side effects refer to levadopa and carbidopa together and are really side effects of the levadopa. Carbidopa is only ever taken with levodopa

[chartist in reply to WinnieThePoo]

If there is a mistake, it is on the part of drugs.com and these other two websites as vomiting is also listed for Carbidopa alone on these three websites which is where I got the information from :

drugs.com/mtm/carbidopa.htm...

MedicineNet also lists vomiting as a side effect of Carbidopa alone :

medicinenet.com/carbidopa-o...

This health library also lists vomiting as a side effect of carbidopa alone :

icacardiology.com/health-li...

Art

[WinnieThePoo in reply to chartist]

Art

Where in the first link (drugs.com) does it say that carbidopa alone causes nausea?

The following side effects may occur when carbidopa is taken with levodopa.

Carbidopa may cause serious side effects. Call your doctor at once if you have:

severe drowsiness;

uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);

worsening of tremors (uncontrolled shaking);

severe nausea, vomiting, or diarrhea;

confusion, hallucinations, unusual changes in mood or behavior;

Read the first sentence.

[WinnieThePoo in reply to chartist]

nope. Both the other sites you quote quite clearly state that carbidopa is only taken with levodopa and the side effects they list are side effects of the combination of the two drugs

[chartist in reply to WinnieThePoo]

You are correct Richard, I stand corrected. I read through two more sites and in describing carbidopa, they seem to combine it with Levodopa because that is the way it is mainly sold here in combination. You can get a carbidopa only prescription, but that seems to be mainly as a carbidopa dose adjustment to Sinemet or similar or a more controlled dose to go with levodopa.

Carbidopa can increase the bioavailability of Levodopa and levodopa can cause vomiting. MP contains levodopa and the increased bioavailability of the levodopa from the addition of carbidopa may be the cause of the vomiting, not the carbidopa itself. Two possible remedies might be to reduce the carbidopa dose further or reduce the MP dose a little at a time.

Art

[WinnieThePoo in reply to chartist]

I think you're on the money this time!

[HekateMoon in reply to chartist]

Bensezaride???

[chartist in reply to HekateMoon]

Benserazide is also a decarboxylase inhibitor as is Carbidopa, but Benserazide has a faster rise and decline in plasma level compared to Carbidopa which seems like it might be potentially more of a problem in this instance of vomiting with MP noted in the original post.

onlinelibrary.wiley.com/doi....

Look at the graph for a visual illustration of the comparison to Carbidopa. The faster plasma level rise at 30 minutes seems like it could potentially increase the potential for vomiting that Little Willow (LW) reported around 30 minutes after taking Carbidopa. On the right side of the graph you can see that Carbidopa maintains a higher plasma level for a longer period of time which could explain why LW reported up to 5 hours of on time whereas Benserazide plasma concentration has declined very significantly at just 3 hours which could potentially result in reduced on time.

Art

Comparison of Benserazide and Carbidopa plasma concentration over time.

[HekateMoon in reply to chartist]

thank you, Art...

[bandmember]

Have you tried Domperidone? I vomited constantly when I started on Madopar. I needed it for a month or two until I adjusted. Four years in now and no problems.

[Raphaekg]

My MDS also recommended additional carbidopa to combat the vomiting from Sinemet. Didn't help at all. Like Bandmember suggested, only domperidone helped. It is a prokinetic agent, helping to combat slow gastric motility. If you live in the US, you will have to be "creative" to get it, since it is not FDA approved. After 13 years of living with PD, I still need to take a half pill of domperidone with my sinemet. As gastric motility has gotten markedly worse over time, it is still an essential part of my medication regime. Since domperidone has cardiac side effects, my MDS asked me to have a comprehensive cardiac workup before taking it.

[GrandNan]

good morning - my husband takes 3 brown Macuna from Barlowes . He eats a piece of toast 1st, to get something in his stomach and waits a few minutes.

And from our reading on this site: he takes the green tea extract along with 2 quercetin, which we get from VitaCost -I believe each capsule has 250 mg. This prevents nausea 99% if the time.

[Tayogi]

I take that exact mucuna with carbidopa, it’s the only thing I take to manage symptoms. I’m positive you are taking too much. When I was figuring out my dose I bought these tiny tsps on Amazon. They start at 1/4 tsp and go down to1/63tsp. I either buy the mucuna in powder or capsule. So I open the capsule and currently the amount of mucuna I take in the morning is 1/16 tsp+1/64tsp it lasts about 6 hours and I take it with very tiny amounts of carbidopa I cut it in 8ths and take one of those, I bought a scale and always weigh the piece of carbidopa to 0.20, so I think it may be 2 mg. I make my own mucuna capsules but I’m always adjusting my dose depending what my body tells me.the second dose is slightly smaller currently at 1/64tsp+1/32tsp it only lasts 3 hours so I’m think on going back to the previous dose 1/16 which lasted 4 h. This is the smallest amount I’ve taken. The amount of mucuna in each barlowes capsules is 1/4tsp + 1/32tsp which is what is started with last year in February . So my current dose is: morning 1/16+1/64 at 7:30 which is about 81mg of l-dopa second dose at 2 or 3 ( I wait to get a slight tremor to take the second dose- I wait til first dose starts to wear off) currently smaller but I’m pretty sure I’m going back to 1/16 which is 65 mg l-dopa. I get nausea a few days per month only in the morning and that’s the days right after my period. Hope this helps and let me know if you have questions. Also, I do this on my own, in only use the neurologists to get carbidopa.

[1LittleWillow in reply to Tayogi]

Wow, OK, I'll try that immediately. Thanks! I have to use SO much without the carbidopa that I didn't think 1 capsule would be too much, but that makes sense because the effectivenesss is incredible.

[Tayogi in reply to 1LittleWillow]

it is extremely effective. If you saw me you would know that I’m dealing those pesky symptoms. I’m so grateful I found the best relief. I can’t wait to hear how it goes with you.

[DavidHeaf in reply to Tayogi]

Tayogi wrote '...my current dose is: morning 1/16+1/64 at 7:30 which is about 81mg...'

How do you convert volumetric values (1/16 tsp etc.) for the powder to metric weights of the powder? Please could you give the conversion factor that you use. (The conversion from powder weight to L-DOPA weight is of course easy, assuming that all batches of Barlowes mucuna extract contain 40% L-DOPA.)

[Tayogi in reply to DavidHeaf]

My conversions are ballpark. So, in the barlowe’s bottle it says the serving size is one capsule and it says that the capsule is 650 mg of mucuna powder and contains 40% l-dopa which would be 260 mg of l - dopa in a capsule, so, I opened one of the capsules and measured how much in tsps it contained, I believe it was around 1/8 tsp and a little more. ( I can’t remember exactly the amount, it was so long ago). So, I know that 1/8tsp plus a little more of mucuna contain around 260 mg of l-dopa. That is the baseline that I use for conversions. Right now I’ve lowered the dose and I’m taking two doses of 1/16 tsp a day. Each 1/16 tsp capsule contains around 65 mg of l-dopa.

I hope this is helpful, let me know if you have any other questions. 🌸

[Tayogi]

oh, and i also took barlowes mucuna with EGCG tea extract and quercetin but it just wasn’t reliable enough. For context I’m 35, have had symptoms for about 10 years. Only took c/l for a week and use cannabis in between doses and at night after the second dose wears off.

[1LittleWillow in reply to Tayogi]

I also use THC for sleep, but I can't use it during the day. If I take a large enough dose to control my tremor, it makes me too groggy to function.

When I take Barlowe's with the carbidopa, the effectivenesss is amazing. I really hope I can figure it out.

[Tayogi in reply to 1LittleWillow]

If I figured it out you can too!

[1LittleWillow]

I love this forum so much. It's been the best source of information and assistance since my diagnosis. You are all wonderful. Thank you!

[CaseyInsights]

Here is my response from two years ago on this issue re your post “Update on Sinemet Nausea and Fatigue”

### My understanding, based on post on this site, is Manuca is difficult to dose.

So here is a prepackaged Manuca/Levadopa combo which my spouse use to replace her neurologist prescription Sinemet 25/100. The product is called DopaBoost. She has been using it since June 2019.

Patient Information here -

designsforhealth.com/produc...

Purchase here-

amazon.com/gp/product/B004L...

The only problem we have with this product is our insurance would not accept a claim on this expenditure🌹###

Have you tried this. It is simple and effective. She still use this without the issues you experience.

Thread here -

healthunlocked.com/cure-par...

[1LittleWillow in reply to CaseyInsights]

I just realized I never responded to your comment, Casey (sorry, we were on vacation and then I forgot).

I tried DopaBoost (and thanks again for the recommendation), but it didn't work for me. It's been quite a while, so I'd have to dig through my notes to see why... it either didn't do much, or it made me nauseous. Thankfully, I'm currently having great success with the Barlowe's Brown plus carbidopa. I'll post about that soon.

[1LittleWillow]

On vacation now, having terrible time using HU with my phone. I'll update when we return home and can use laptop. Great success (2 days) w/TINY dose of carbidopa. Hoping it continues.

[evanchen]

Hello, it is impossible to buy carbidopa products in our country. I have eaten six kinds of Mucuna products and added green tea GTH, all of which can only last for three hours. Levodopa and carbidopa share very little vomiting. I have had Parkinson's for ten years. I have been thinking about buying a separate carbidopa. You can buy Cabidopa over there. Can you help me to buy a bottle of 25mg Cabidopa . I pay you, my Messenger account is junyu.chen.5437, please add contact, thank you!

[1LittleWillow in reply to evanchen]

I replied to your message. I can't purchase carbidopa from a store. It is only available here in the United States if you have a prescription from a doctor.