Supplemental Carnitine and Exercise


Carnitine (L-3-hydroxytrimethylammoniobutanoate) is an endogenous molecule with
several established roles in mammalian cellular metabolism.1 All of carnitine’s
known biochemical functions are mediated via the reversible transfer of
activated carboxylic acids (“acyl” moieties) from coenzyme A to carnitine.
In this way, the formation of acylcarnitines is critical for the mitochondrial
oxidation of long-chain fatty acids, and formation of short-chain
acylcarnitines protects the cell from potentially toxic acyl-CoA accretion.2
Thus, cells contain both carnitine and acylcarnitines, with the
acylcarnitines composed of a spectrum of specific acylcarnitines
(i.e., acetylcarnitine). Total carnitine refers to carnitine plus all

In humans, carnitine is derived from a variety of dietary sources, particularly dairy and meat
products. Carnitine can also be synthesized in humans with lysine providing the carbon backbone of
the molecule. Available evidence indicates that the biosynthetic capacity of carnitine is adequate to
meet the needs of most people, and dietary intake is not required. In contrast, pathophysiologic
conditions exist in which carnitine supplementation is of clear therapeutic value.

Carnitine metabolism is highly compartmentalized in humans. Tissues contain
widely varied amounts of total carnitine, ranging from 60 mmol/L in plasma
to 4,000 mmol/kg in skeletal muscle. Additionally, the distribution of the
carnitine pool between carnitine and acylcarnitines can vary among tissues,3
and tissues have distinct turnover rates for carnitine.4

Carnitine Metabolism During Exercise

The bioenergetics of exercise require an enormous increase in muscle adenosine
triphosphate (ATP) production and related changes in substrate fluxes.
Carnitine, because of its intimate relationship with the coenzyme A pool,
reflects many of these metabolic changes. As the ATP demands increase with
increasing exercise workloads, a metabolic transition workload, termed the
lactate threshold, is reached.5 At workloads below the lactate
threshold, lactate does not accumulate in plasma or muscle, the respiratory
exchange ratio (RER) remains approximately 0.80, and the exercise can be
sustained. At workloads above the lactate threshold, lactate accumulates,
the RER reaches 1.00, and performance at the workload cannot be sustained.
At rest, the skeletal muscle carnitine pool contains a distribution of 80-90
percent carnitine and 10-20 percent acylcarnitines (primarily short-chain
acylcarnitines). At workloads below the lactate threshold, the distribution
of the muscle carnitine pool is not altered. However, as workloads exceed the
lactate threshold, the muscle carnitine pool is redistributed into
acylcarnitines so that 50-70 percent of the pool is in the form of
acylcarnitines.6,7 This redistribution is not normalized 60 minutes after
a 30-minute exercise session above the lactate threshold. It is now clear
that this increase in acylcarnitine content is the result of
acetyl-CoA accumulation, leading to acetylcarnitine generation.8
Importantly, the dramatic changes in the muscle carnitine pool during exercise
are not reflected in the plasma or urine compartments.

Rationale for use of Carnitine to Enhance Exercise Performance

The relationship of the carnitine pool to the critical metabolic processes of bioenergetics has led to much speculation about the potential benefits in normal humans of supraphysiologic carnitine levels. The possible mechanisms by which carnitine could have an effect are varied and include the following:

  • Enhancing oxidation of fatty acid, a critical substrate, during exercise
  • Preserving muscle glycogen during exercise, a factor potentially related to fatigue resistance

  • Shifting fuel substrate use toward glucose, thereby decreasing the oxygen requirement for the workload-defined ATP requirement

  • Replacing the carnitine depleted by acetylcarnitine formation

  • Enhancing acetylcarnitine formation, lowering acetyl-CoA content, and, thus, activating pyruvate dehydrogenase

  • Improving muscle fatigue resistance

  • Replacing carnitine losses that occur during aerobic training

  • Increasing oxidative capacity in skeletal muscle.

    Each of these concepts can be justified on theoretical grounds and has been partially validated through in vitro or limited animal studies. However, equally persuasive arguments can be constructed as to why they would not apply to exercise in normal subjects receiving carnitine supplementation. Thus, experimental evidence in humans is required to address this issue before conclusions can be reached.

    Considerations in Carnitine Dosing in Normal Humans

    Carnitine is available for use in intravenous or oral preparations.
    In pharmacological doses, the bioavailability of oral carnitine is 5-15 percent.
    Elevations in plasma carnitine content after carnitine dosing lead to rapid
    increases in urinary carnitine elimination. Further, the muscle compartment
    reaches steady state with respect to the plasma carnitine pool only slowly
    and is quantitatively much larger. Thus, use of carnitine supplementation
    to perturb the muscle carnitine pool is problematic, given the body’s handling
    of the compound.9

    Carnitine is well tolerated in humans, and administration of the pure L-isomer has been associated with no serious side effects. Gastrointestinal symptoms, including diarrhea and cramping, are the most frequently noted adverse effects of the compound.

    Effect of Carnitine Supplementation on Exercise Performance in Normal Humans

    Clinical studies of carnitine’s effect on exercise performance or metabolism during exercise have usually involved small numbers of patients; lacked comprehensive evaluation of the patients’ carnitine, metabolic and performance status after receiving carnitine; and have used varied populations (i.e., athletes versus nonathletes). Given these considerations, it is difficult to draw generalized, definitive conclusions concerning carnitine supplementation. Several conclusions do seem justified based on the available data in normal humans:

  • Acute or chronic carnitine administration can increase plasma carnitine concentrations.

  • Acute carnitine administration, or daily administration for a period of 1-2 weeks, does not increase skeletal muscle total carnitine content or the response of the muscle carnitine pool to exercise.

  • Administration of carnitine for 4-6 months to athletes engaged in training prevents a training-associated decrease in muscle total carnitine content, and may increase total carnitine content compared with baseline measurements.10

  • Carnitine, whether administered intravenously or orally, acutely or chronically, has no consistent effects on key metabolic parameters during exercise or exercise performance.16-18

  • Carnitine administration for months may modify mitochondrial enzyme expression during training of athletes.11

  • No well-designed clinical trials are available demonstrating that carnitine enhances exercise performance in normal subjects.

    These conclusions do not justify the use of carnitine to improve exercise
    performance in normal humans. Multiple studies exist, with results of which
    could be interpreted as at least partially positive, particularly in athletes,


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    Avatar Written by Eric P. Brass MD PhD

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