Acetyl-L-Carnitine Review

[NeoV]

I've been busy digging through studies, although superficially, to come to an understanding of Acetyl-L-Carnitine's (ALCAR) mechanism of action (if it is indeed effective at all). Since the claims regarding heart issues have been "debunked" for some time now, and nearly 14 years have passed since the initial study on ALCAR, I think it's a good time to re-evaluate it. After looking at a number of studies (all which I've been able to find) several stood out to me in particular which I want to discuss here. The link to my list of studies is below.

STUDIES THREAD

The state of the research
- To date, there is only one study on Peyronie's and ALCAR that showed positive results, and two more on Propionyl-L-Carnitine (PLC), the most recent was double-blind which showed no results. This is discouraging, since the first two studies were not double-blind. However, we do not know the exact difference between ALCR and PLC and it is specifically ALCAR that our mitochondria use and that triggers the CrAT gene. Below are my findings I deemed relevant to Peyronie's from reviewing research on ALCAR on other things.

From my initial review of the literature, ALCAR may be effective because it

   
• Reduces TGF-β, the fibrogenic cytokine behind Peyronie's.¹
• Reduces interleukin 6 which is responsible for a range of autoimmune inflammatory disorders as well as diabetes.² Deficiency of Carnitine has also been shown to cause an autoimmune response in rat gut models and is thought to be linked to improper gene encoding in Crohn's disease.³
• Increases nitric oxide signaling via activity of the gene carnitine acetyl transferase (CrAT), thus improving endothelial health, particularly in those who's gene has been impaired who are at risk of a range of problems.⁴ Poor endothelial function = hypoxia = fibrosis. Also relevant to the vascular trauma model. Impaired CrAT activity would be interesting to study in depth in relation to Peyronie's
• Is analgesic (a pain killer), by up-regulating mGlU2 metabotropic glutamate receptors,⁵ with its vast body of research being on neuropathic pain.
• NEW - Vasculoprotective effects possibly due to it inhibiting advanced glycation end product (AGE).

^{references
1 http://www.biomedcentral.com/1471-213X/14/21
2 http://www.ncbi.nlm.nih.gov/pubmed/24239319
3 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480427/
4 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565262/
5 http://www.ncbi.nlm.nih.gov/pubmed/11961116
6 http://www.ncbi.nlm.nih.gov/pubmed/25636076}

I invite everyone to discuss their own thoughts as well as mine on ALCAR and to look at the studies I have provided on the studies thread. Let me know if you find other information or studies worth noting. Almost all studies lack their full versions and if anyone has access or is able to find them please let me know. And of course, feel free to dismiss, criticize, or expand. There are many interesting studies in that thread worth looking into.
 

[Jonbinspain]

I'm no scientist, but yes, ALC is the one supplement that I feel has done more for me than any other. Obviously, it's difficult to be sure when taking many different oral supllements, but that's my impression.

I take probably 3-4 grams per day in powder form.  

[dplookin]

Jonbinspain.........Thank you for your post.  I used ALC for 3 months and got no results, but due to your posting, I just ordered 3 more months worth of ALC, but of a better brand instead of a cheap brand.  I will give it another chance.  I hate to give up on something that is so important.   dplookin

[Jonbinspain]

dplookin;

Good luck, hope it helps. I do take a few different supplements, so I can't be 100% positive about the ALC, but the evidence is there that it can help with Peyronie's. I take it in conjunction with R-Alpha lipoic acid. They have a synergy and together are a very powerful anti oxidant in the body.  

[ryanchan]

Dr. Bella

Sent me research results that showed L-Catharine to be helpful and decreases curvature by an additional 15 degrees! The caviete is those results only come when it is used in-conjunction with injection.  

[NeoV]

Dr. Bella was probably referring to the second study on my list

Directly related to Peyronie's
2007 - Comparison of vitamin E and propionyl-L-carnitine, separately or in... - PubMed - NCBI (Propionyl-L-Carntine, not effective)
2002 - Oral propionyl-l-carnitine and intraplaque verapamil in the therapy... - PubMed - NCBI (propionyl-l-carnitine, effective)
2001 - Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie's d... - PubMed - NCBI (Acetyl-L-Carnitine, effective)

That was on PLC, not ALCAR specifically. The bad news is that the 2007 study that was longer and much better controlled, showed no improvement with PLC than placebo on curvature or plaque size even after 5 months. While this is discouraging and very bad for the case of PLC, the implications on ALCAR are not yet understood. Moreover, the initial SINGLE study on ALCAR was not exactly a well done study. It leaves us with a lot of doubt, but I'm not ready to dismiss ALCAR, or even PLC just yet.

[NeoV]

Update!

TMAO, the dreaded byproduct of ALCAR supplementation, and ALCAR's "vasculoprotective" effects. Advanced glycation end products (AGE) and it's receptor (RAGE) appear to be related to vascular disorders and inflammation. Pentox and ALCAR block it.

Oral L-carnitine supplementation increases trimethylamine-N-oxide, ... - PubMed - NCBI

Questions:

1. What does advanced glycation end products (AGE) and it's receptor (RAGE) have to do with fibrosis and inflammation? Pentox is listed as a substance that is known to block AGE as well. Could it be another important factor in Peyronie's caused by vascular injury or dysfunction?

2. So, what exactly is the verdict? Is TMAO from ALCAR supplementation actually dangerous? I sure wish I knew.

[ryanchan]

Sounds Like its BAD!!

I think the study is saying, because it creates protective layers in the arteries, its good for those with HD.

In our case, we don't want that right? Because it will thicken and stiffen our veins making our peyronies worse?

Thats how i understood it

[NeoV]

Yes Ryan, there was a big upset about ALCAR in 2013 or so regarding red meat consumption and ALCAR potentially raising heart attack chances. While ALCAR has been defended by numerous authors, this is the first study I know that followed up.

I wish I knew the dose, and the TMAO levels. Human studies with details are needed.

If you go to my ALCAR studies page you can see that it has all sorts of endothelial and vascular healing properties, its only TMAO that is the problem, and even the above study concludes with something like "The role of TMAO needs to be looked into", since in actuality, no study has really looked at TMAO alone as a cause of heart problems, it may just be correlated.

Still, I was afraid of ALCAR for this very reason for years! Finally after reading some articles I thought I might as well hop on boat.  

[Mending the Bend]

[The post below had previously been a separate topic, but I thought it was more appropriate in this thread]

Hi all,

I saw some user-friendly research reports and videos recently which pointed to potentially harmful results of taking Acetyl-L-Carnitine supplements, which I thought worth sharing. I'm simplifying this for summary, but it seems that taking carnitine oral supplements (or consuming it via meat) causes certain gut bacteria to form a substance called TMAO - which can lead to atherosclerosis. Atherosclerosis, as we know, restricts blood flow in our penile arteries, resulting in ED. (Among other things, like heart attack and death.)

Report: Avoid Carnitine and Lethicin Supplements | NutritionFacts.org

Video: Carnitine, Choline, Cancer and Cholesterol: The TMAO Connection | NutritionFacts.org

So, maybe ease up on the meat consumption. Or at least watch those ALC supplements. I personally found them to be of little to no help and have completely stopped taking them.

For those interested in deeper reading on TMAO and diet (it's more complicated than carnitine and meat), check out this:

Report: Does Carnitine From Red Meat Contribute to Heart Disease Through Intestinal Bacterial Metabolism to TMAO? - Weston A Price

FYI, as a result of my focus on supplement and diet research over the past 18 months of dealing with Peyronies Disease, I recently started eating an entirely plant-based diet. No meat, dairy, or eggs. I think it's helping greatly with inflammation, as well as my blood lipid profile. It's taken some adjusting, but I feel great. Probably more fit than I've been in years.

Mending the Bend

[goodluck]

I found it very effective for pain.    I am past the high levels of pain and have since stopped taking it.  Mostly because it can interfere with thyroid hormones.

See a summary here on Alcar which one of our members generously compiled.

Oral Treatments General Information - Peyronies Society Forums

[Jonbinspain]

Don't confuse Acetyl L  Carnitine with just L-Carnitine. They're two different substances.  

[pizzaman]

It turns out that fish has drastically higher levels of TMAO than red meat, but higher fish consumption is overwhelmingly associated with better heart health (and better health in general). The current consensus seems to be that the fish oils "cancel out" the negative effects of TMAO.

So, if you're concerned about about ALCAR and TMAO, take some fish oil, which you should probably be taking anyway.

Anecdotally, I started taking about 2g/day of ALCAR almost immediately after my Peyronie's symptoms began. I believe this may have limited the disease progression for me. Pain continues for a while, but I have very little (~5°) curvature when fully erect, and no noticeable loss of length.