Q:  L-carnitine & Liver Irritation from Depakote ER

Dear Dr. Phelps,
I am relatively new to this website, but have found your information very helpful.  I was diagnosed with BiPolar NOS in January 2004 and have been doing a lot of research trying to determine the best approach for reducing my rapid (daily) cycling (anxiety/irritability, depression, mania).

I took up to 1,000mg/day of Depakote ER for one month and was relatively cycle-free during that time.  It was wonderful!  However, during the time I was on the Depakote ER, I experienced gassiness, indigestion, stomach bloating, and slight (about 5 pounds) of weight gain.  These symptoms worsened with each increase in my dosage.

After I had been on 1,000mg/day for about one week, I had what felt like a gallstone attack (I had my gallbladder removed in 1999, but remember what it felt like to have stones pass or get stuck).  My liver enzymes were elevated 2-3times normal.  At the request of my medical doctor, I discontinued the Depakote for one week and then had the liver tests taken again.  My enzymes were back to normal/good.

Since the Depakote ER worked so well at controlling my rapid cycling, I wanted to get back on it.  I recently started back at a lower dose (500mg/day) and added one teaspoon of prescription L-Carnitine.  I am also taking 500mg of Keppra each night.  This combination is definitely helping control/reduce my rapid cycling and is helping me fall (and stay) asleep at night.

I think the L-Carnitine supplement is helping reduce the gassiness, indigestion, nausea, and liver irritation caused by the Depakote.  I am still experiencing slight weight gain and abdominal/stomach bloating, though.

I think I may have a Carnitine deficiency (even without the Depakote ER) because I am a vegetarian and my blood tests show slight anemia.

Do you know if L-Carnitine helps reduce the liver irritation caused by taking Depakote ER?  If so, can I buy the over-the-counter Acetyl version to save money or do I need to get the prescription L-Carnitine version?  Also, I have read that I should be taking 1 to 2 grams per day (since I am a vegetarian with anemia).  Does that sound right to you?

Thank you for providing so much helpful information on this website.  You are helping so many of us who struggle to manage our BiPolar so we can function in society.

Sincerely,
Wendy 

Dear Wendy -- 
Thanks for the occasion to review this rather complex subject of valproate (Depakote in the U.S.) and carnitine.  

First of all, yes, there is at least one case report of carnitine helping someone get past liver irritation, e.g. this report by Romero-Falcon. 

Secondly, let's have a few "basics" about carnitine, some of which may make some sense to you though it's in full medical jargon, and I'll pull out some important details: 

Carnitine is an ammo acid derivative found in high energy demanding tissues (skeletal muscles, myocardium, the liver and the suprarenal glands). It is essential for the intermediary metabolism of fatty acids. Carnitine is indispensable for beta-oxidation of long-chain fatty acids in the mitochondria but also regulates CoA concentration and removal of the produced acyl groups. AcylCoAs act as restraining factor for several enzymes participating in intermediary metabolism. Transformation of AcylCoA into acylcarnitine is an important system for removing the toxic acyl groups. Although primary deficiency is unusual, depletion due to secondary causes, such as a disease or a medication side effect, can occur. Primary carnitine deficiency is caused by a defect in plasma membrane carnitine transporter in muscle and kidneys.

 Secondary carnitine deficiency is associated with several inborn errors of metabolism and acquired medical or iatrogenic conditions, for example in patients under valproate and zidovuline treatment. In cirrhosis and chronic renal failure, carnitine biosynthesis is impaired or carnitine is lost during hemodialysis. Other chronic conditions like diabetes mellitus, heart failure, Alzheimer disease may cause carnitine deficiency also observed in conditions with increased catabolism as in critical illness. Preterm neonates develop carnitine deficiency due to impaired proximal renal tubule carnitine re-absorption and immature carnitine biosynthesis. Carnitine stabilizes the cellular membrane and raises red blood cell osmotic resistance but has no metabolic influence on lipids in dialysis patients. L-Carnitine has been administered in senile dementia, metabolic nerve diseases, in HIV infection, tuberculosis, myopathies, cardiomyopathies, renal failure anemia and included in baby foods and milk. (Evangeliou)
 

On the Linus Pauling Institute site, which has lots of information about carnitine in fairly plain though advanced english, as well as some nice diagrams that go right back to medical school (yipe), note that almost all of the "secondary" conditions described above are treated with L-carnitine.  But there is one set of studies, their references 29-32,  that used acyl-L-carnitine.  I don't know if that's the acetyl version you're talking about as cheaper.  You might try writing the Linus Pauling folks and see if you can dig up an answer.  Copy me if you learn something good, okay?  

Dr. Phelps

Published June, 2004