Free/Esters Carnitine Ratio Test

Your cells use a small carrier molecule to move fats into the part of the cell that burns them for energy. Some of those carriers sit free and ready for the next load. Others are mid-job, bound to a fatty fragment they have already grabbed. This number compares the two. When it runs high, it means too much of your pool is tied up and not enough is free, even if your total carnitine looks fine on paper.

Of all the numbers on a carnitine panel, this ratio is one of the most informative for spotting functional carnitine insufficiency. It is a value clinicians use to identify people who may benefit from treatment when total carnitine sits in the normal range. If you are looking at a carnitine panel and want one number to focus on, this is often it.

Why a Ratio Beats a Single Number

Total carnitine can be misleading. The body holds carnitine in two pools: free (unused, ready to work) and esterified (already bound to a fatty fragment). Total is just the two added together. Someone can have a perfectly normal total while their free pool has been silently shrinking and their bound pool has been silently growing. The total stays steady, but the system is no longer balanced.

The ratio catches this imbalance directly. A value of 0.4 or greater means too much of your pool is tied up with fatty fragments and not enough is free to grab new ones. That pattern shows up in dialysis, in some people on long-term valproate (especially children and those on multiple anticonvulsants), in some inherited fatty acid oxidation disorders, and in critical illness. It can be an early warning that the system is backing up before total carnitine moves out of range.

What Sends the Ratio Up

A high ratio almost always means one of two things. Either your free pool is being depleted (by a medication, dialysis, or an inherited transporter problem), or your cells are producing more bound carnitine than they can clear (because something is blocking the final steps of fat oxidation). In both cases, the result is the same: not enough free carnitine left to keep fat moving into your cells efficiently.

The clearest example comes from people on maintenance hemodialysis. Their total carnitine is often normal, but free carnitine runs low and bound carnitine runs high, producing a ratio above 0.4. The dialysis procedure pulls free carnitine out of the blood faster than the bound forms, so the bound forms accumulate. One large series found that nearly 87 percent of maintenance hemodialysis patients met the ratio-based definition of carnitine insufficiency. This pattern is the basis for FDA-approved L-carnitine supplementation in dialysis patients, even when total carnitine looks reassuring.

The Valproate Connection

If you take valproate (Depakote, Depakene) for seizures, mood, or migraines, the carnitine panel is worth tracking. The picture varies by who is studied. In adults on long-term valproate alone, free and total carnitine often remain in the normal range, but specific acylcarnitines accumulate, suggesting that valproate is interfering with fat oxidation enzymes even when the bulk numbers look fine. In children, especially those on multiple anticonvulsants or treated for one to twelve months, free carnitine more clearly drops and the esters-to-free ratio shifts upward.

The clinical concern is that this metabolic shift may contribute to valproate's rare but serious complications: liver toxicity and high blood ammonia. The ratio is one of the signals that something is changing in fat handling, sometimes before any other carnitine number moves.

When the Ratio Is Misleading by Design

There is one important exception. In primary carnitine deficiency (the rare inherited disorder where the kidney transporter leaks carnitine into urine), free carnitine and bound carnitine both fall in proportion. The ratio stays normal even though the absolute values are very low. So a normal ratio is not always reassuring on its own. It needs to be read alongside the actual free carnitine value to make sense.

This is why no single number on the carnitine panel tells the whole story. The ratio is the most informative for catching insufficiency in the people who have it, but the absolute free carnitine value is what catches the rare cases where everything is uniformly low.

Reference Ranges

Reference values vary slightly by lab and assay. The most widely cited cutpoint comes from the National Institutes of Health Office of Dietary Supplements and clinical biochemistry references.

These thresholds are drawn from published research and clinical reference labs. Your lab may use slightly different cutpoints. Compare your results within the same lab over time for the most meaningful trend.

When Results Can Be Misleading

The ratio responds to short-term metabolic shifts faster than most lab values. The timing of your draw matters more here than for many other tests. The biggest contributor to a misleading single reading is fasting state, since prolonged fasting itself shifts the body toward fat burning and pushes the ratio up.

• Recent prolonged fasting: more than an overnight fast can push the ratio up by shifting your body toward burning fat. Test after a normal meal pattern, not after a long fast.
• Intense exercise the day before: vigorous workouts can temporarily raise the ratio by stressing fat oxidation in muscle.
• Acute illness: any major metabolic stress can shift the ratio temporarily. Wait until you have recovered before testing.
• Pivampicillin and certain other antibiotics: these drugs combine with carnitine to form bound forms (such as pivaloylcarnitine) that distort the ratio without indicating a true metabolic problem. The effect resolves after the course ends.