The Effect of Curcumin on Idiopathic Park... - Cure Parkinson's

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The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

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Abstract

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

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35 Replies
park_bear profile image
park_bear

Great research! Actual controlled human study cleverly using skin biopsy instead of brain biopsy for checking aSyn.

in reply to park_bear

BP, do you take it? Is it okay with cinnamon or will that compete for absorption? I sometimes add Moringa to it as well , all mixed in to a repulsive goat milk yogurt concoction.

🌸 Newbie

park_bear profile image
park_bear in reply to

I am not taking it at this time but that could change. Cinnamon with yogurt appeals to me but I am not sure I would appreciate curcumin added to it. No competitive absorption as far as I know but I have not studied this matter.

in reply to park_bear

I recommend the full fat plain yogurt instead of a grain for reducing insulin spike from grains and improved bioavailability from taking with a fat. Alternatively, I also recommend having the curcumin on cauliflower rice with olive oil and pepper.

Do you know the form and dose used for the study? I can look for that info but am asking first in case you already have. I know it has very poor bioavailability so I combine it with black pepper and oil. I’m not sure if this is not advisable but I take it just in the powdered (not pill) form along with my cinnamon.

Supposedly this “meriva” form / additive helps with absorption.

Does anyone know if there is a consensus on what form truly has the best absorption?

Meriva
park_bear profile image
park_bear in reply to

According to the study fulltext the treatment was:

"2 g per day of curcumin as curcumin phospholipids as Meriva (1 g b.i.d. of Maxicur) for 1 year"

I did not find any reference to Maxicur, but Meriva is apparently manufactured by:

indena.com/us/product/meriva/

In addition to the source you mention is also available from Thorne.

amazon.com/Thorne-Research-...

Also, Meriva is not straight curcumin but rather contains related compounds. More about it here:

pubmed.ncbi.nlm.nih.gov/214...

"levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures."

academic.oup.com/jnen/advan...

"Meriva is standardized to contain 18%–22% of curcuminoids including curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) dispersed in a phospholipid matrix. The remaining amount of Meriva (78%–82%) contains the delivery system (phytosome ) that is needed to increase the bioavailability of curcuminoids.

Sydney75 profile image
Sydney75 in reply to

My gastro MD from India said must be taken with food for proper absorption. We have been using the Liquid Turmeric from Qunol that includes 1000 MG Curcumin extract with andother 1290MG of Proprietary Tumeric support complex: Glycerine, acacia gum, xanthan, gum, guar gum, Ascorbic Acid, and piper nigrum. Not sure what the gums do, take with dinner. Latest kidney function tests normal. She (gastro) indicated this can cause several gastrointestinal issues, if it happens take a break. (She said the same thing about berberine). Also to be careful with this and taking ibuprofen.

From the Natural Database:

Dermatologic

Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause contact urticaria (79985,97432). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).

- Gastrointestinal

Orally, turmeric can cause gastrointestinal adverse effects (107110,107112), including constipation (81149,81163,96135), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430), diarrhea or loose stool (10453,17952,18204,89720,96135), dyspepsia (17952,89720,89721,96161), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430), epigastric burning (81444), and tongue staining (89723).

- Hepatic

Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury. There have been at least 60 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 8 months, most of which resolved upon discontinuation of the turmeric supplement. Oftentimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122). It is not clear if this contributed to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122).

Note Thorne's Curcumin Phytosome - Sustained Release (formerly Meriva) does contain phytosomal curcumin.

park_bear profile image
park_bear

Study results were not quite as good as I had hoped. The treated group did show less deterioration according to UPDRS than the untreated group, but the untreated group started from significantly lower baseline. Some of the other measures were better - the skin biopsy ("samples" below) did show improvement in the treated group, although it did not reach statistical significance. Also, the untreated group was allowed to increase levodopa medication whereas the treated group was not, which would have created an adverse bias in these numbers.

Study results
in reply to park_bear

But if the untreated group was assessed at the end with more medication than they started the trial with, assessing how they are doing is completely inaccurate and misleading. Have a misunderstood? This is absurd. I hope I have misunderstood. They should assess both placebo and treated subjects at the beginning and end of the trial unmedicated otherwise they are also unintentionally assessing how they are responding to meds but to increase meds and then assess is just ridiculous.

The past year has been such an eye opener for me. I am by now means the smartest tool in the shed but I used to put doctors, researchers, scientists on pedestals far above the laymen. I now realize how they don’t communicate amongst each other. The trials are frequently poorly constructed. They are trying to determine if interventions work for a disease with disproportionately little research to determine the causes of the disease. Symptoms are presumed to have the same cause. That’s lame. You can arrive at the same destination via different routes. A neurological disorder is called a movement disorder when in reality it is when an abundance of bio markers have been ignored for YEARS that finally it gets so bad that movement is affected.

I’m ranting because damn this is frustrating.

I don’t want to be a patient researcher but I now have no faith that a neuro will do a darn thing to slow my progression let alone find any way of stopping or reversing it.

I left UNC so mad last week that the neuro was literally shaking. Maybe it’s contagious! 😡

Continue on determined people! We will prevail! This bleeping disease will not take me down.

kevowpd profile image
kevowpd in reply to

I do not understand why anyone looking to track disease progression would ever measure the participants in the on medication state. It simply isnt possible to get good quality data when the symptoms are masked.

in reply to kevowpd

Agreed. We butt heads due to personality differences but we often agree. “simply isnt possible to get good quality data when the symptoms are masked.”

Exactly and that is so basic and obvious that I am dumbfounded by how trials are conducted.

kevowpd profile image
kevowpd in reply to

I just hope that the big well funded trials, the ones where people have considered success sufficiently plausible that they are willing to throw money at it, are doing this stuff in a way that will produce quality data. Youd hope so but the more i read the less confident i am.

park_bear profile image
park_bear in reply to

No you have not misunderstood. Here is the actual text:

"The untreated group showed worsening of all clinical scales despite the increase of L-dopa dosage (Table 2). The curcumin-supplemented group, which was not allowed to increase L-dopa dosage..."

Agreed that it creates an invalid comparison.

With regard interacting with MDs, it helps to understand that MD education trains doctors to practice medicine which is different than practicing research. As medical practitioners they are expected to follow their agreed-upon authorities without question. This works to keep a large and varied population of MDs from trying crazy ideas. This fails badly to the extent that the agreed-upon authorities are stuck in suboptimal ideas, particularly the idea that prescription meds can do no harm, and supplements can do no good.

On the other hand, crazy ideas are a lot more common than we might like to think. Here is a recent one that MDs and other researchers who should have known better embraced:

healthunlocked.com/cure-par...

in reply to park_bear

Regarding curcumin trial, the results would have appeared (been) better had they not allowed the placebo arm to be assessed with increased dosage of CL. Had the placebo arm not increased CL like those receiving Curcumin then, the difference between the placebo and those who had been receiving curcumin would have been larger. Am I correct? This therefore improves the plausibility that curcumin can be beneficial. Turmeric as used in cooking contains a lot of oxalates which can contribute to kidney stones. But, some supplemental versions do not from what I have read. I have yet to determine which curcumin supplements. I hope the Meriva version is one.

Regarding the uric acid trial you linked to, it was absurd. I responded with a leading uric acid researcher from Colorado.

I’m considering stopping my turmeric consumption for the sake of my kidneys and am hoping to source a version similar to that used in the trial. But only if what I stated above is correct regarding the benefit being greater (at least to some degree) than reported in the trial.

park_bear profile image
park_bear in reply to

Yes you are correct! The actual benefit is understated, although we do not know by how much.

in reply to park_bear

Do you think you might give it a trial period PB? It would be so great if we could arrange groups to synchronize trying new things for specific durations and obviously without other additions. This would not be scientific per se but better than just N of 1.

Buckholt profile image
Buckholt in reply to

Whilst these trials continue to offer hope, I am always slightly downhearted when outcomes have to be determined by statistical analysis. I think what most of us are waiting for is a response from a new therapy which is no obvious, so overwhelming that the results don’t need careful mathematics to determine success. But that the participants are just plainly doing better!

Despe profile image
Despe in reply to Buckholt

A M E N to that Buckholt. We are not scientists to interpret statistical results nor do we have the time to read the lengthy scientific trial methods and results. We are just interested in CLEAR results, beneficial or not???

In the meanwhile, here is what hubby uses after reading and searching.

amazon.com/Ultracur-Curcumi...

Do the trial results convinced me to switch to Meriva, absolutely not.

park_bear profile image
park_bear in reply to

A good idea. If you want to gather up a group for this purpose I suggest making a separate post.

Unfortunately curcumin has not worked for me for reasons unrelated to Parkinson's.

cielserin profile image
cielserin in reply to park_bear

Bonjour, Chaque jour je mets un curcuma que je coupe en tranche fine dans ma salade avec un petit morceau de gingembre car j’ai plus confiance dans la nature que dans la chimie, ai je raison ? Merci pour vos réponses

park_bear profile image
park_bear in reply to cielserin

If it is helpful for you, then that is good.

Si cela vous est utile, c'est tant mieux.

Nikosmom profile image
Nikosmom in reply to

I totally agree with your frustrations about the so called experts. I gotten to point of not trusting any of their opinions It has become a lonely and star-less road for me. The more I learn the more i am confused with no place to turn for concrete answers Parkbear has become a resource for me in evaluating research findings.

park_bear profile image
park_bear in reply to Nikosmom

Thanks for the kind words!

There will always be statistical analysis. That said, I agree – a clear-cut benefit is what we are looking for. The kind of thing you are talking about would be a greater than six-point improvement in the UPDRS part three as compared to placebo.

Stillstandingstill profile image
Stillstandingstill in reply to Nikosmom

In their defence, conventional medical experts have to work within clear boundaries of tested and proven good practice. Saying that, as a person with PD, I too feel frustrated with the limitations of current treatments and speed of developments. Even the accepted definition of PD that gets continually wheeled out is woefully out of date. In the meantime, while we wait, many of us are conducting our own little single case studies.🙃

Sydney75 profile image
Sydney75 in reply to Stillstandingstill

I agree, it is also about liability.

Despe profile image
Despe in reply to

Good on you! We have an appointment with our MDS next month. The only question I will have to ask is "Is there any disease modifying medication you could prescribe?" Nothing else to ask as there isn't a damn thing any neuro or MDS can do for PD patients.

rescuema profile image
rescuema in reply to

Read the book "Sickening" by John Abramson and it'll enlighten how seriously corrupt the pharmaceutical industry is, and why we need serious reform.

"The inside story of how Big Pharma’s relentless pursuit of ever-higher profits corrupts medical knowledge—misleading doctors, misdirecting American health care, and harming our health.

The United States spends an excess $1.5 trillion annually on health care compared to other wealthy countries—yet the amount of time that Americans live in good health ranks a lowly 68th in the world. At the heart of the problem is Big Pharma, which funds most clinical trials and therefore controls the research agenda, withholds the real data from those trials as corporate secrets, and shapes most of the information relied upon by health care professionals.

In this no-holds-barred exposé, Dr. John Abramson—one of the foremost experts on the drug industry’s deceptive tactics—combines patient stories with what he learned during many years of serving as an expert in national drug litigation to reveal the tangled web of financial interests at the heart of the dysfunction in our health-care system. For example, one of pharma’s best-kept secrets is that the peer reviewers charged with ensuring the accuracy and completeness of the clinical trial reports published in medical journals do not even have access to complete data and must rely on manufacturer-influenced summaries. Likewise for the experts who write the clinical practice guidelines that define our standards of care."

amazon.com/Sickening-Pharma...

simonasays profile image
simonasays

Just wanted to say the back and forth between you too is so helpful. Im not sufe whether i will add this to my dad's regimen but i myself taking curcumin 1 gram for inflammation and migraines and find it helps. Re: medical doctors, particularly ones that work in teachinv hospitals, the publication of research makes you marketable and valuable. The quality of the research many times can be lacking.

Condor13 profile image
Condor13

Sorry but any post which starts with:"There are currently no standardized therapies for Parkinson disease (PD). "

Is written by someone lacking awareness.

In my 60 years of medical practice, one of the most amazing things I saw, was in the early 70's, was a man unable to leave his bed with PD, and waiting to die, then Levodopa became available and he was back at work four weeks later.

Since then I have seen hundreds of "promising" treatments come and go. As a PWP, I share the frustration , but Levodopa is still the drug of choice.

Gcf51 profile image
Gcf51

I have been taking Curcumin with BCM-95 for about 9 months. It is touted as highly absorbable. It contains essential oils too. I take one 650 mg softgel a day. The supplier indicates approximately 26 mg Turmerones. Ar- Turmerone is supposedly good for PD. Seems to be helping with my aches and pains. Can’t really say helps with my PD.

walmart.com/ip/Curcumin-650...

MarionP profile image
MarionP

This was a pretty good study, the science was clear and but for the small sample and high dropout rate (almost 50%) the design was a good one. For those familiar with actual science. The design was very good for a preliminary effort and was clear and standardized enough to be replicated, and the tools have a very high degree of reliability. Small conclusions and generalizability to larger and different groups.

For those used to looking through the science lens: this one has really decent actual science and a very nifty design, just that it was small, but the important thing is that it is the sort of study that would be successful in getting money for more elaborate larger trials with people who have earlier onsets, later onsets, what it might do for people's symptoms as opposed to stopping or preventing the disease itself, all extremely expensive and needing to attract big money to properly look into from good science. But clinical promise in the meantime means people could just start trying it.

As to the science, the experimental design is really nifty, something we don't often get to see. These authors definitely know how to do serious, justifiable relevant science. Very nice measurement tools. Small but distinct mechanism demonstration of positive direction with symptoms and at least suggest the potential to investigate further the alpha synuclein hypotheses at least for symptoms...which is rather exciting because further down the road it could be involved in looking at alpha synuclein misfolding as a potential cause of the substanta nigra dopamine producing cells die-off, meaning one could help discern whether alpha synuclein is part of the cause or is just something that makes cell functioning impossible as a side effect...especially good for looking at PD and the Lewy Body dementias...that is a big deal because huge research money has been consumed with alpha synuclein...which thus can't be spent on looking into other things. But if I was in school right now it is actually interesting enough to be worth doing one's dissertation in there somewhere. One of the best studies I've seen in a long time, and particularly the demonstration of ability to cross the bbb barrier with an oral preparation and get into the cerebrospinal fluid. This could attract some of the very big money usually can't be gotten for what's already out as a dietary supplement, again that's a good thing. Best to look at the discussion section for very reasonably limited conclusions and mentions of the weaknesses of the study. Meanwhile something very nice here is that it might actually lead to some sort of help with symptoms, so maybe a substitute or adjunct to levodopa. It's really rare to get a preliminary study that hits on so many research and clinical cylinders like this one does. Just really impressive study.

But there is also, somewhere I saw, maybe a downside for some people who have liver disease, diabetes, gallbladder issues, bleeding problems, GERD, iron deficiency, liver disease, arrhythmia, hormone problems. So talk to a doctor first please. And beware that a lot of curcumin or turmeric sold can be adulterated with a heavy metal, I think it might be lead, because it gives a nice yellow color so unscrupulous manufacturers can, I think have, put it in there to cut it. So the fact that it isn't, or doesn't have to be I guess, manufactured to pharmaceutical standards, could be a bit of a gamble if you use a great deal of it.

rescuema profile image
rescuema in reply to MarionP

This is a good reminder for anyone who has anemic tendencies, so watch your intake. I have this problem with Life Extension's Curcumin Elite, which might be a bit too bioavailable at 45x.

lifeextension.com/vitamins-...

Iron Deficiency Anemia Due to High-dose Turmeric

ncbi.nlm.nih.gov/pmc/articl...

Boscoejean profile image
Boscoejean in reply to rescuema

I think the puzzling thing about all this is that I have read that it is believed that some people with Parkinsons have too much iron in their system so would the turmeric help someone who was in this position or would it just cause the person to become anemic?

Boscoejean profile image
Boscoejean

Initially we were told that Meriva was a better form of curcumin but since then there are a couple other forms that are being mentioned like micronized curcumin and another supplement called super bio-curcumin and I am trying to find out what it is that is supposed to make that one better. So here is what the site says about the super bio-curcumin: "Curcumin is a bona-fide super food—but its hard to absorb. So we make our curcumin formula with the highly-absorbable BCM-95® Bio-Curcumin® extract. BCM-95® is up to seven times more absorbable than standard curcumin. BCM-95® stays in your bloodstream longer as well."

enjoy2013 profile image
enjoy2013

I agree with MarionP.

Talking about the next step, hopefully, rather than pharma / venture capital money, maybe this study could be noticed by CPT and the MJFF, and a few philanthropist, that would be a great case study of alternative evidence-based medicine!

However, to my opinion, what will determine next steps is the levodopa treatment discussion.

The method paragraph describes what happened:

"...Twenty-one patients agreed to start the curcumin supplementation (supplemented group): 2 g per day of curcumin ... for 1 year, maintaining stability of the dosage of L-dopa and/or dopamine agonists. ... Nineteen PD patients did not agree to undergo to the study protocol as they felt more protected by increasing the traditional (i.e. L-dopa) therapy (untreated group as controls...".

It is not easy as patients to stick to a fixed treatment regimen for 12 months.

That's how the researchers adapted to people lack of interest to join the study. I guess that many wanted to be free to change their levodopa dose as needed. I would.

So they 'randomised' those patients to be in the control group, ie get no experimental treatment for a year.

I think they anticipated it would be harad to find people to join the study.

It is not easy to tell people with a progressive disorder:

"Hey, listen, I would like you to commit to my next trial, which is going to assess how effective is 1 full year of treatment with curcumin in slowing the progression of your disease, Parkinson, how safe it is and how well tolerated it is.

Truth be said, I and the team, we believe curcumin will be found to be effective within a year of treatment, and we think is very safe and well tolerated. Furthermore, we believe it could be a great option as you can buy it for relatively little money in a food supplement shop on the high street or online.

By the way, we are asking you to undergo CSF collection (please let me stick this huge needle in your spine, and keep it there for 2-3 minutes whilst I collect your CSF), skin biopsies and various tests, and to stick to the same treatment all year long.

The chances are 1 out of 2 that you get all that program , with no curcumin for a whole year because you are in the placebo group."

Whilst you wonder what's your opinion, I am on my way out to buy some curcumin. I cannot afford to wait.

This is why the looked for a way to make it acceptable for everybody.

The treated group gets the curcumin straight away but can't change their ldopa dose.

The untreated group doesn't get curcumin but continues life as if they never heard of it, with standard of care.

The researchers, well, they get a trial. Rater-blinded, not randomised, but as Marion said, really great trial.

So I would like to propose we forgive them because actually, they designed a study that is very respectful of patients, which is quite refreshing. As someone said in a previous post, everybody can see that if the treated group could change their levodopa dose probably they could use it in the analysis to emphasize the treatment effect (if curcumin works).

They clearly knew that when they discusssed the design and wrote the protocol. Rather than treating us like lab animals, or go for an uncontrolled study, they sacrificed some design features in the protocol to make it fair and acceptable.

I think it's visionary.

Finally, remember that the phase III trial would require much more many pwPD. So we may never see the phase III. Not because of grid or lack of shiny profits on the horizon, but simply because

Really, who would join?

Instead, let's join their discussion, on "What is the alternative to traditional evidence-based medical decisions algorithms and evidence-based regulatory decisions?"

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