Andrographolide for GCA?

Hello everyone,

As usual I am being my scientific self and doing research with our good friend Dr. Google. As always, I really appreciate the guidance I receive here and the helpful advice, experience sharing, and wisdom everyone has to offer.

I was researching an herbal or natural supplement that has demonstrated in lab studies its effectiveness in inhibiting certain cell growth pathways by interfering with key gene transcription factors that cause the production of pro-inflammatory proteins and thus preventing these pro-inflammatory proteins from causing abnormal cell growth (intimal hyperplasia) in the walls and linings of arteries as is the case in vasculitis.

The one supplement I found is called andrographolide, and is found in high concentrations in the plant andrographolis paniculata.

I found two useful articles in my research:

1. ncbi.nlm.nih.gov/m/pubmed/1...

2. cdn.intechopen.com/pdfs/417...

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

The first one above discusses the effectiveness of andrographolide in reducing cell growth pathways leading to vasculitis and arterial inflammation. The second one discusses andrographolide's demonstrated strong efficacy in interfering with cell growth pathways leading to rheumatoid arthritis. The cell growth pathways related to RA and GCA are quite similar, and both involve the elevated production of a type of pro-inflammatory protein called interleukin-6 cytokine, which is known to cause inflammation in vasculitis. To demonstrate the effectiveness of andrographolide, the second study even showed that ESR in patients with rheumatoid arthritis decreased significantly while taking andrographolide at a dose of 45 mg/day the form of Andrographolis paniculata, which in certain herbal forms contains up to 30% andrographolide. The third article above demonstrates again the effectiveness of andrographolide in inhibiting the inflammatory effects of interleukin-6, which is a fundamental cause of inflammation in GCA. Tocilizumab is an immunosuppressant drug currently being used to stop the binding activity of interleukin-6 cytokine, which is the cause of the inflammation, and is now being used in clinical trials for GCA treatment in conjunction with steroid therapy. If andrographolide can suppress interleukin-6 activity in an effective manner similar to (but most likely not nearly as powerful and also with much fewer side effects and much less expensive in comparison) the effects of Tocilizumab (a pharmaceutical), then does it make sense that andrographolide could be used in conjunction with prednisone therapy to treat GCA? Has anyone else thought of this or spoken to a doctor about it?

I just bought Andrographis paniculata (which contains 30% andrographolide) online from the website below:

ediblescience.com/store/p/4...

and I am going to start taking it to see if my symptoms can improve more rapidly or even without steroids for several months. Even if this herbal supplement can help safely maintain remission of GCA long term I am willing to try it. It is not expensive at all and has demonstrated its effectiveness in laboratory and clinical studies so I would assume it could have some beneficial therapeutic effect towards alleviating GCA symptoms and blood inflammatory indicators (ESR an CPR). Interleukin-6 (IL-6) can be measured in blood plasma with a simple blood test and is typically always elevated (up to 92%) in all untreated patients with GCA, so the trends and correlations between IL-6 inhibition and the reduction of inflammation in GCA leading to possible remission in conjunction with steroid therapy make sense to me. From what I have read, andrographolide may prove effective in long term GCA treatment not only by treating a significant underlying inflammatory cause of GCA (increased IL-6 production) and leading to faster remission rates but also by allowing steroid tapering to begin more quickly, shortening the total length of harmful steroid therapy, and preventing flares or relapses of GCA over the course of one's lifetime after remission has been achieved.

I just wanted to share these findings with everyone and see if anyone has any comments or questions in this wonderful open forum.

Cheers,

Devin

[PMRpro Ambassador]

Please do check with your doctors about using this supplement if they decide to put you onto any medication - if it does what you say it does then it can also interfere with other medications or even cause serious problems.

Forgive me for being sceptical but "and has demonstrated its effectiveness in laboratory and clinical studies" is to be found on many websites where no such thing has ever been done under the normal controlled conditions required for mainstream medicine. Purchasing supplements on the internet - or from a health food store - is fraught with risks as they do not need to be tested rigorously nor is their manufacture subject to any controls and the ingredients are often not declared accurately.

[Hidden in reply to PMRpro]

Hi PMRpro,

Thank you for your insight. As I've already talked to them about different natural remedies to ailments, the doctors I have seen here in USA frequently are not aware of herbal supplements and their effects, so it may be up to me to have to investigate drug interactions. I do not smoke or drink alcohol, and I do not take other medications regularly. Obviously if I experience negative side effects from an herbal supplement I will certainly stop taking it and go to the emergency room if necessary. This can happen of course with steroids (fractured hip from osteoporosis for ex) and has already happened with Tocilizumab in trials and studies (patient developing deadly infectious disease like endocarditis). I believe a natural supplement has the potential to offer the best treatment for a long-term illness due to relatively few side effects and at least enhance or bolster the effects of standard therapies used in conjunction.

As for purchasing supplements over the Internet, I am aware that much of the information is not regulated and that the ingredients in these supplements have not been analyzed for purity or validated by a government organization. Nonetheless, if you can investigate the information quality available, you will find reliable information. The particular blend of Andrographolide that I purchased is a proprietary blend known as Paractin, and was a result of the double blind study conducted in Chile. This same blend is what I ordered according to their information. Of course, it could be a lie and I could be ingesting sugar pills, but I work in a laboratory myself and can perform a quality control check myself to identify the structure of andrographolide from a mass spec analysis I am not afraid to at least try something different, because the one time one person takes that risk, it has the potential to only help others, even if the result is negative. Information is our greatest power with combating illness.

I realize that many studies can claim whatever information they like, fake results, and not be checked it cross-examined by legislative organization such as the FDA. The articles I have listed are from renowned academic universities. To be honest, I do not see any reason why an academic organization would fake results. Academic institutions like universities are obviously some of the most unbiased sources of information, do not care about making money, and care first and foremost about the quality of research for the sake of quality research. In contrast, much of what is approved by the FDA (Food and Drug Administration) is fraught with corruption and politics based on a desire of pharmaceutical companies to make the most money at the expense of the patient having to take the medication as their only treatment option in many cases for a rare illness. The very fact that one has to wait for the clinical trial results is unacceptable. Additionally, I, being out of the age range for which the clinical trial was administered, would not be allowed to take such potentially beneficial medication because I am not in the studied cohort.

[PMRpro Ambassador in reply to Hidden]

"I do not see any reason why an academic organization would fake results. Academic institutions like universities are obviously some of the most unbiased sources of information, do not care about making money, and care first and foremost about the quality of research for the sake of quality research. "

For someone who says they are a scientist you seem a bit naive! There have been plenty of faked results in science - and before you say I'm just another member of the public, I and my husband have been part of the scientific community since long before you were born. If you think university departments don't care about making money how do you think they exist? Publish, publish, publish, sometimes poor science, so they can get their next grant.

Nor should you fall into the trap of believing because something is "natural" it has no side effects. If it is strong enough to do something - it also has the potential to cause side effects and interactions. Deadly nightshade is pretty natural!

"The very fact that one has to wait for the clinical trial results is unacceptable" - there are good reasons for clinical trials and them being done properly. As some young men of your sort of age in the UK would tell you - look up the TGN1412 study at Northwick Park Hospital in London.

You have already fallen in one trap - believing you have found something that wasn't known about in this community. The role of IL-6 is not unknown in PMR/GCA, nor is the possible role of toxcilizumab, a drug which has been mentioned quite often on the UK forums. There is not yet any proof it works as well as pred - and therein is an ethical conundrum. You cannot try another unproven drug instead of pred - it might not work and your patient might end up blind. You can only use it alongside pred and see if it improves the result. And that takes time.

The vast majority of the people are in a situation where they can only have medications that are approved by their insurance of whatever sort. I think you might find it rather difficult to get this pretty pricey drug paid for by your insurance until the results of the clinical trials are published and - probably - extended somewhat. Your insurance company will look at their documentation and tell you they will fund corticosteroids - because that is the recognised mainstream approach and it works reliably. Until you know other drugs work at least equally as well and with fewer risks then you are left with only two options really: take the recognised drug or reject it and face the risks associated with the disease.

Good luck.

[Hidden in reply to PMRpro]

I believe I am the first person to suggest novel andrographolide thank you. University studies really do not care about making millions and millions of dollars. The professors I know from my work in and outside of college are the most anal and calculating people I know, are only interested in research for the sake of benefiting the world and of course rely on government grant funding to conduct their research, but government grants on the order of hundreds of thousands of dollars maximum (just enough to conduct the research) are much much less than the potential money a company can make for-profit for pharmaceutical. I am certainly not naive for recognizing the unbiased information published by universities. University researchers are in large number altruistic and very much concerned with the quality of their work as opposed to making money. Any funding provided to a university research project will go to funding the research, so any desire to make more money is only out of a desire to expand and help validate quality research. I respect your opinion, but I believe university work is by far the least biased and by far the least likely to be corrupt.

[JAMESJACKS in reply to PMRpro]

question: where do you think dr's get their info from...the pharma co's ... they read the same studies you pull up on pub med etc... do your own homework.. its your body.

[Celtic PMRGCAuk volunteer]

IL-6 and its possible link to PMR/GCA has been the subject of research among the medical experts over recent years, and is, no doubt, ongoing.

Whether or not you decide to take Andrographis paniculata is obviously your choice, Devin, but it is very unwise to purchase any such drug or supplement from the internet at any time - certainly, if steroids are prescribed for you following your biopsy, you will need to get advice from a good pharmacist before taking it alongside steroids, as with any other drug/supplement.

As for Toxilizumab in the treatment of GCA alongside steroids, the clinical trials have been completed and we are still awaiting the findings.

[Nap1 in reply to Celtic]

Hi

Been following Toxilizumab but was not aware that the study was complete. Will you publish the findings on this site for us whenever you get the results. I can only pray that it is positive. The prednisone has warn me out, with the worst being muscle weakness which is peaking right now, still at 40. Learning from this site that my reductions must be slower was disheartening. So a little help from a new ( proven) drug would mean a lot. Thank you for your generous advice.

[PMRpro Ambassador in reply to Nap1]

You might be interested in this:

gsk.com/en-gb/media/press-r...

[Nap1 in reply to PMRpro]

Interesting. If they are on phase lll was phase I and il just for RA? And we're these 2 phases successful if you know? If TCZ was successful, and we might have that information soon, then I understand that the cost would be in the vicinity of $3,000 a month. I was told this by my former Rheumatologist. Perhaps he was guessing (that's why he is former). New drugs in the US are ridiculous. But so is my Actonel and that's over 10 years old. Thank you for keeping us informed. Marilyn

[PMRpro Ambassador in reply to Nap1]

Phase 1 and 2 are usually to assess safety - i.e. make sure it won't kill you/make you very ill. Phase 3 is to assess if it works in the specified illness in a moderate size population.

TCZ is still a very new drug under patent protection which adds to the cost. But production costs for the biologics are high so the price will remain highish anyway. I doubt he's guessing - TCZ is already used for RA patients and while the US system leads to silly prices being asked for nowhere else is much better.

What I've posted is what I know - I suspect they are still in the middle of the RA stuff and they tend not to tell the world at that stage.

[Nap1 in reply to PMRpro]

I think you are correct. It is being used on trials for GCA, but I hadn't heard that the trials were over. What you are saying, I think, is that the RA trials are over yes? Not the GCA. I do understand the price of medicine and what it cost to develop a drug of this nature. I would do without a LOT to pay for a drug that would get me off the pred. sooner. It's a killer. Am I right that the trials are not over.

[PMRpro Ambassador in reply to Nap1]

I'm not even sure the RA trials are over and the GCA trials aren't not even underway - they have to recruit patients to star, there aren't that many anyway so trials take years when you need a minimum number to do the stats. Plus you have to have follow-up to be sure that, even if it apparently works, that the effect is sustained. And it may be that any NEW drug turns out to be a "killer", literally or metaphorically, in the long run. The sure fact with pred is there is little they don't know about it.

I've just realised we may be talking at cross-purposes: the toxcilizumab GCA trial is finished, the results are still being processed so not published yet.

Sirukumab trials in GCA have not yet been started - a lot of paperwork locally comes first. Even the first patient won't be finished with for 3 years because of the structure of the study. There will be a minimum number of patients required - and it is ONLY for patients who have had a positive biopsy so they are 100% sure it is GCA they are looking at. Both new and relapsing patients are eligible so if anyone having a flare and with a positive TAB is interested it is worth asking for information about the trial.

[Celtic PMRGCAuk volunteer in reply to Nap1]

Nap, I attended the Vasculitis Symposium held in London in April, where we were informed that the Toxilizumab GCA trial had been completed. As soon as the results are published I am sure they will be available on our Charity's website pmrgcauk.com/ and mentioned on this forum.

[Nap1 in reply to Celtic]

Thank you. I look forward to the results

[piglette]

Devin do listen to what the others say and also I think you should think twice about giving up steroids for a trial.

[Hidden in reply to piglette]

Hi piglette,

I would never stop taking a medication such as prednisone if it is recommended by a physician. And I of course would find out drug interactions before putting something into my body that can affect your immune system, which is what Andrographolide effectively and largely safely, does.

[piglette in reply to Hidden]

Oh good, I misunderstood you.

There is a warning on WebMD re andrographolide:

Some Internet vendors offer andrographis products that contain extra amounts of an active ingredient called andrographolide. Some of these products are almost 30% andrographolide. However, be careful; the safety and effectiveness of andrographis preparations with high andrographolide content are unknown.

[professort]

Hi, Devin -- I stumbled across your post from 2 years ago, by searching on Google for "Andrographolide for GCA", wondering about the same possibility. I didn't see any further post from you in this thread as to how your experiment went. . . Did you try Andrographolide and did it help? (The interleukin-6 inhibition looked like a positive to me. However, one further question I had was that Andrographolide also is an immune booster -- and I wondered if there was an issue with taking an immune booster with an automimmune disease. . . Thanks for any update you can provide!