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
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
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)
Institute site, which has lots of
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?
Published June, 2004