Hello,

I would love some thoughts on this.

I have been diligently studying Neurotalk and every Mrs. D post possible and was just about to start Acetyl-L-Carnitine (ALCAR) to accompany my R-Lipoic Acid and Coenzyme Q10 to tackle my Chemo Neuroapthy (CIPN). (I finished Taxol and Carboplatinum last November).

I then came across this recent fairly well respected large study (409 patients across many treatment centers) saying that ALCAR did not improve and in fact slightly worsened CIPN neuropathy.

It is the first large study of ALCAR for CIPN. There are a handful of very small studies stating that ALCAR helps CIPN and is also safe / does not encourage cancer tumor growth.

Even the authors say that they were surprised by the results. Brings to mind the research joke, you know you are truly finding the truth when you don't like the results.

From other editorials, it appears that others in the medical community also find these findings discouraging. They seem to respect how this study was conducted and express their dismay that once again, when they think there might be something for CIPN, the evidence says otherwise.

Although this study was for preventing/curtailing CIPN by taking it during chemo, I now reluctantly feel like we just don't know enough about it and I should just stay away from it even though for me it is for repairing nerves post chemo.

Also, I am spooked about supplements in general. Perhaps we just don't know enough about how RLA and CoQ10 interact with Chemo Neuropathy and I should play it safe and not take those as well?

Also, as much as I adore all the Neurotalk contributors and have been so grateful for every post, please forgive me if I am starting to have doubt ... perhaps there just isn't many Neurotalk contributors with chemo neuropathy? Perhaps most are diabetics and other types of neuropathy, and the supplements that have been used for years with other types just don't cross over to chemo neuropathy?

So my questions are:
1) Do you agree that I should play it safe and stay away from ALCAR?
2) Do you have some reason why you think other supplements that haven't been well studied with Chemo Nueropathy, such as RLA and CoQ10, are safe and I should continue with them?
3) Do you think that Neurotalk is mostly diabetics and I have to be extra careful in assuming that many of the discussions here cross over to Chemo Neuropathy?
4) For non-CIPNer's, do you think these results cross over to other types of neuropathy?

Big thanks for any thoughts,

Natalie

P.S. Please forgive me if this study has already been discussed here .... I did a search and couldn't find it mentioned.



Here is the studies and related editorials:


"Conclusion There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy. "

A Double-Blind, Randomized Phase II Study to Evaluate the Safety and Efficacy of Acetyl-L-Carnitine in the Prevention of Sagopilone-Induced Peripheral Neuropathy
The Oncologist 2013, 18:1190-1191.
full text of study available online:
http://theoncologist.alphamedpress.o...f-50887211d6e5



"Acetyl-L-Carnitine Increases The Risk and Severity Of Taxane Induced Neuropathy:

Contrary to promising results from earlier studies (preclinical and smaller human studies), a large randomized trial found that patients who received acetyl-L-carnitine (3,000 mg per day) during their taxane-based chemotherapy for breast cancer actually developed neuropathy more frequently and had more severe neuropathy compared with those who took a placebo.

The bottom line: Don’t take acetyl-L-carnitine to reduce the risk of taxane-induced neuropathy…it doesn’t work.

This is yet another study that makes the same point as I made above, that we need to be cautious in our adoption of new therapies before they have been proven safe."

http://www.integrativeoncology-essen...mo-neuropathy/




"Acetyl-L-carnitine and prevention of chemotherapy-induced peripheral neuropathy: can anything work?

The current study describes a well-executed, prospective, placebo-controlled, double-blind, randomized trial. ....
Preclinical data with ALC examined the prevention of axonal damage and mitochondrial dysfunction and appeared promising [2], However, together with other studies (Table 1), the current report indicates ALC will not be an effective therapy forchemotherapy-induced PN, and other strategies will need to be pursued. "

The Oncologist (Impact Factor: 4.1). 01/2013; 18(11):1151-2.
free full text available online:
http://theoncologist.alphamedpress.o...5-190ea69fdf06
or also:
https://onchd.alpha.intstrux.com/art...y-can-anything



Other summary of study:
"Chemotherapy: Supplements—for better or worse?"
Nature Reviews Clinical Oncology 10, 426 (2013); published online 18 June 2013; doi:10.1038/nrclinonc.2013.106
Full text available:
http://www.readcube.com/articles/10....inonc.2013.106

I won't be able to look this over in depth
Until I return from vacation.

You can look up the authors however and
See if they are supported by big Pharma
Or other monies.

Supplement research is always spotty. This
Is because it is difficult to weed out
Dietary and other lifestyle factors.
3000mg a day is also higher than the 2000 mg
I have often seen.

Here's the sponsor of the first study: Sponsor(s): Bayer HealthCare Pharmaceuticals

Not certain about the other one.

Regarding your questions:

1) Do you agree that I should play it safe and stay away from ALCAR?

Since you are no longer on any chemo, I don't feel you need to play it safe. I don't think you would use the doses they are talking about anyways. Also know that as you heal, you may find an increase in symptoms for a week or two and then more relief. As the nerves wake up, new sensations happen.


2) Do you have some reason why you think other supplements that haven't been well studied with Chemo Nueropathy, such as RLA and CoQ10, are safe and I should continue with them?

I don't think you will ever find a good, solid research for this. It's too costly, and too difficult to design a study where the people all started from the same nutritional baseline and were able to maintain it throughout their treatment. You don't know if any in the study were diabetic or had other issues. It is very difficult to combat the ill effects of chemo with supplements. Those drugs are so strong and disruptive. And everyone responds differently to chemo.

3) Do you think that Neurotalk is mostly diabetics and I have to be extra careful in assuming that many of the discussions here cross over to Chemo Neuropathy?

The short answer is 'no'. My husband's PN is chemo induced and he has benefitted greatly from what we've learned here. In fact, there's a huge crossover to bone marrow failures, which is what he had. I found that everything I learned here, could also be applied to his healing after treatment.


Hope this helps.

Nice post, Marlene. Thank you.

I would also like to point out that patients
In those studies probably hover in middle
Age or older for the most part.

The study does not mention allowing or screening
For prescription drug use. Statins,
And certain drugs for UTIs and URIs
Cause neuropathy and could cloud
The conclusions. These drugs are more
Common in middleaged and older patients.

These forums are to help people decide
For themselves after reading the literature,
Which way to choose.

I myself have seen women use Flaxseed oil
Mixed with cottage cheese (to provide sulfurous
Amino acids) sail thru chemo without
Developing PN. One even reversed a beginning
Spinal metastasis.

But you won't find a "study" on that (that I know of).

Big thanks Mrs D and Marlene.

Yes, I think we can all agree that Mrs. D deserves vacations.


"3000mg a day is also higher than the 2000 mg"

Yes, I was surprised the amount of was so high (a dose of 1,000 mg three times per day. They state this was based on earlier studies success.

"You can look up the authors however and See if they are supported by big Pharma Or other monies. "

The list of people and institutions involved is quite lengthy, which makes me think there would be less bias (other than the general big bias towards big pharma) but perhaps I am naive.


Yes, thanks for these thoughts.


Even though this study was about taking ALCAR during chemo, I am still spooked because it highlights that we just don't know the mechanism of chemo neuropathy and so maybe we just don't really know if this helps or hurts.

I think of Hypocrities great advice to doctors "DO NO HARM" ... meaning at least don't make the situation worse.

Here's a quote from the study:
"... we found that at 24 weeks, there was a significant detrimental effect of the ALC intervention ..."
"Several other clinical trials of nutritional supplements that showed promise in preclinical and observational studies were found to be detrimental in clinical trials."

I found this to be true with other things I was on the verge of taking and then later found it, it actually made the situation worse or helped cancer cells grow.

Perhaps once you've just gone through ovarian cancer, one becomes skittish and extra cautious.

Another quote from study:
"Use of complementary medicine, particularly antioxidant sup- plements, is widespread among patients with cancer.27 Among 663 participants in the Long Island Breast Cancer Study who completed follow-up interviews, 401 (60.5%) reported using antioxidants during adjuvant treatment, and of these, 278 women (69.3%) used high doses.28 Americans spend 􏰂 $12 billion per year on dietary supple- ments.29 This is of particular concern, given the paucity of evidence of benefit and the increasing evidence of harm."

This is a good point .... Antioxidants can be tricky and can actually do the opposite of what you want depending on how taken ... especially during chemo.

I'm all for natural cures.

Mrs D doesn't have to answer this now .... but I am curious what guidelines come to mind as to when she makes the leap of faith and when she thinks it might just cross over into the unknown of possibly causing more harm than good.

Yes, I know this is a tough question.

Here are some other very recent studies / editorials written after this study which reference the study. I'd like to know what they say about the "Carnitine Worsens" study.

Does anyone know any tricks to getting access to these very recent articles?

I've tried all my usual hunts for "full text" versions to no avail.


------------------------------------------------

Cancer Treat Rev. 2014 Aug;40(7):872-82. doi: 10.1016/j.ctrv.2014.04.004. Epub 2014 Apr 18.
Chemotherapy-induced neuropathy: A comprehensive survey.
Miltenburg NC1, Boogerd W2.

Current Treatment Options in Oncology
Date: 14 Aug 2014
Therapeutic Strategies for Cancer Treatment Related Peripheral Neuropathies
Deirdre R. Pachman MD

Appropriate Use of Complementary and Alternative Medicine Approaches in Gynecologic Cancers.
Current Treatment Options in Oncology (Impact Factor: 2.42). 01/2014; DOI: 10.1007/s11864-013-0269-x

Mitotoxicity in distal symmetrical sensory
peripheral neuropathies
Gary J. Bennett, Timothy Doyle and Daniela Salvemini
Bennett, G.J. etal. Nat. Rev. Neurol. 10, 326–336 (2014); published online 20 May 2014; corrected online 1 July 2014; doi:10.1038/nrneurol.2014.77

For those interested in ALCAR for CIPN, I gathered the previous studies below just to have them in one place for reference.

Professor Bianchi is near me in Switzerland and has agreed to meet with me in the past.

I was thinking of asking him what he thinks of this latest big study contradicting his small study below.

Does anyone have any suggestions of good questions to ask if I get to be in front of him?


----------------------------

Chemo and ALCAR


Here are the small studies that proceeded this larger study, which they say they used as a foundation.

These seem to be less respected for reasons such as too small, uncontrolled, purely theoretical, based only on rats, etc,



Bianchi G, Vitali G, Caraceni A, et al: Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer 41:1746-1750, 2005

Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.
A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy.

Pisano C, Pratesi G, Laccabue D, et al: Pacli- taxel and cisplatin-induced neurotoxicity: A protec- tive role of acetyl-L-carnitine. Clin Cancer Res 9:5756-5767, 2003

JXiao WH, Zheng H, Bennett GJ: Characteriza- tion of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel. Neuroscience 203:194-206, 2012

Zheng H, Xiao WH, Bennett GJ: Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy. Exp Neurol 232:154-161, 2011

Xiao W, Naso L, Bennett GJ: Experimental studies of potential analgesics for the treatment of chemotherapy-evoked painful peripheral neuropa- thies. Pain Med 9:505-517, 2008

Jin HW, Flatters SJ, Xiao WH, et al: Preven- tion of paclitaxel-evoked painful peripheral neuropa- thy by acetyl-L-carnitine: Effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Exp Neurol 210: 229-237, 2008

CNS Drugs. 2007;21 Suppl 1:39-43; discussion 45-6.
Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review.
De Grandis D.



This study says that ALCAR doesn't seem to decrease the effectiveness of taxol or carboplatinum and does not seem to cause ovarian cancer cells to proliferate:

Effect of acetyl-l-carnitine on ovarian cancer cells' proliferation, nerve growth factor receptor (Trk-A and p75) expression, and the cytotoxic potential of paclitaxel and carboplatin.
Gynecol Oncol. Mar 2009; 112(3): 631–636.

I have been taking at minimum 3000 and often 4000 mg ALCAR for well over 4 years for Swine Flu Vaccine induced neuropathy. I personally believe it has been a tremendous benefit to me personally. Just wanted to chip that in, for what its worth.

Research studies are tricky. The powers that be are often attempting to discount the benefit of supplements.

An interesting tidbit on Bayer, who sponsored the referenced study above:

http://www.naturalnews.com/news_0006...cines_hiv.html

Makes me wonder if they knew Avelox caused PN when they released it to the public?