Oley Foundation

Carnitine -- Who Needs It?

Peggy Borum, PhD
Professor of Human Nutrition and Pediatrics, University of Florida

HomePN patients are encouraged to discuss this article with the physician managing their TPN. Carnitine deficiency is typically not an issue for HEN consumers, because most enteral formulas have carnitine in them.

Everyone needs carnitine to maintain normal metabolic function, though it is not entirely clear who needs a supplemental source of carnitine. Should carnitine be added to parenteral nutrition solutions? And if so, in what concentration? We do not have the data to definitively answer this two-part question. As always, when all the needed data are not readily available, one resorts to "expert opinion." But before getting to opinion, let's distinguish what we know from what remains to be determined.

Carnitine's Role in Metabolism

Carnitine plays many different roles in normal metabolism. It has been known for a long time that everyone needs it in order to use fat for energy and that many foods in the non-vegetarian diet contain carnitine. In a lead article in the January/February 1986 issue of the LifelineLetter, it was noted that most parenteral nutrition solutions do not contain carnitine and that individuals receiving parenteral nutrition solutions for an extended period of time often have lower plasma carnitine concentrations than do individuals who consume carnitine. This statement is still true.

We know that in addition to its long recognized role in facilitating the use of long chain fatty acids for energy, carnitine also has a role in glucose utilization and amino acid utilization. Carnitine is used by the body in the detoxification of many carboxylic acid compounds; an individual may have too high a level of carboxylic acid due to intake of the compound (such as through medication) or due to altered metabolism (increasing synthesis and/or decreasing utilization of the compound). There is a growing body of evidence which indicates that carnitine may have some roles in metabolism that are very different than what have been recognized before, such as a role in membrane repair. Thus an overwhelming amount of data shows that carnitine is important in metabolism and that inadequate carnitine will lead to a variety of symptoms.

Determining Carnitine Status

The usual technique for determining an individual's carnitine status -- measuring total and free carnitine in plasma -- yields only an approximate assessment. The free carnitine value is frequently subtracted from the total carnitine value to obtain a calculated acylcarnitine value, which is used by different investigators in a variety of ways to assess an individual's carnitine status. Investigators are still looking for a method to quantify each individual acylcarnitine in as many different metabolic compartments as possible, because they believe it will make the assessment of carnitine status more accurate. Current techniques for screening inborn errors of metabolism identify many of the acylcarnitines, and progress is being made to make a quantitative acylcarnitine profile readily available for metabolic monitoring -- but we are not quite there yet. The plasma carnitine compartment does not always reflect other metabolic compartments and thus one should use the best chemical analysis of carnitine available to assess as many metabolic compartments as possible. For example, plasma and red blood cells are two different metabolic compartments of carnitine that can and should be analyzed.

When Supplemental Carnitine Is Needed

Carnitine is not a vitamin. Data do not indicate a need for dietary carnitine by healthy young adults. However, there is a great deal of data consistent with the hypothesis that supplemental carnitine is required under special physiological circumstances. Thus carnitine is considered a "conditionally essential nutrient." Parenteral nutrition is probably one of those conditions where supplemental carnitine is beneficial. More data are available for newborns than for adults. But the data are not sufficient for proof, so we are getting into the realm of opinion.

If parenteral nutrition solutions are supplemented, data are clear that it is critical that the supplement be pure L-carnitine. Since much of our experience with carnitine supplementation has been with its detoxification role in inborn errors of metabolism that require pharmacological amounts of carnitine (50 to 100 mg/kg body weight/day), it is tempting to extrapolate that experience to nutritional support with parenteral nutrition. However, the usual dietary intake of carnitine is in the range of 2 to 5 mg/kg/day. Several investigators have shown that hemodialysis patients who receive carnitine supplementation of 2 to 5 mg/kg/day experience beneficial effects that are lost when they are supplemented with 20 to 50 mg/kg/day. Available data do not show a need to supplement parenteral nutrition solutions with pharmacological doses of carnitine unless there is an inborn error of metabolism being treated.

It is my opinion that parenteral nutrition solutions should be supplemented with carnitine at a dose that is similar to the dietary intake of most western countries. I suggest that parenteral nutrition solutions be supplemented with pure L-carnitine at 2 to 5 mg/kg/day. I suggest that plasma and red blood cell carnitine be monitored before supplementation and at four months after supplementation. If the chemical analysis indicates concern about carnitine status, monitoring can be repeated at four-month intervals and supplementation adjusted. Once carnitine status has stabilized, carnitine status should be monitored yearly.

References
1. Arduini A, Denisova N, Virmani A, Avrova N, Federici G, Arrigoni-Martelli E. Evidence for the involvement of carnitine-dependent long-chain acyltransferases in neuronal triglyceride and phospholipid fatty acid turnover. Journal of Neurochemistry. 1994; 62: 1530-1538.
2. Berard E, Iordache A, Barrillon D, Bayle J. L-Carnitine in dialyzed patients - the choice of dosage regimen. International Journal of Clinical Pharmacology Research. 1995; 15: 127-133.
3. Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB Journal. 1992; 6: 3379-3386.
4. Borum, PR. Carnitine in neonatal nutrition. Journal of Child Neurology. 1995; 10: S2-S7 Supplement 2 November.