This article first appeared in the
December, 1995
issue of VRP's Nutritional News
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No information in this article should be taken as a recommendation.
If you have any questions about the relationship between Malic Acid and your
health, seek the advice of a qualified physician.
Malic Acid, Energy, and Fibromyalgia Primary
fibromyalgia (FM) is a condition affecting principally middle-aged women,
characterized by a syndrome of generalized musculoskeletal pain, aches,
stiffness, and tenderness at specific anatomical sites. This condition is
considered primary when there are no obvious causes. Since it was first
described, FM has become recognized as a fairly common rheumatic complaint
with a clinical prevalence of 6 to 20 percent. Additionally, FM has been
associated with irritable bowel syndrome, tension headache, mitral valve
prolapse, and chronic fatigue syndrome. Numerous treatment modalities have
been attempted to treat patients with FM, but unfortunately the results have
usually been poor. The primary reason for this lack of success was undoubtedly
due to our lack of understanding FM's etiology. In recent years,
evidence has accumulated to suggest that FM is the result of local hypoxia
in the muscles. For instance, patients with FM have low muscle-tissue oxygen
pressure in affected muscles, and to a lesser degree the same was found in
other tissues. Muscle biopsies from affected areas showed muscle tissue breakdown
and mitochondrial damage. Additionally, low levels of the high energy phosphates
ATP, ADP, and phosphocreatine were found. It has been hypothesized that in
hypoxic muscle tissues glycolysis is inhibited, reducing ATP synthesis. This
stimulates the process of gluconeogenesis, which results in the breakdown
of muscle proteins to amino acids that can be utilized as substrates for
ATP synthesis. This muscle tissue breakdown, which has been observed in muscle
biopsies taken from FM patients, is hypothesized to result in the muscle
pain characteristic of FM. Malic acid is both derived from food
sources and synthesized in the body through the citric acid cycle. Its importance
to the production of energy in the body during both aerobic and anaerobic
conditions is well established. Under aerobic conditions, the oxidation of
malate to oxaloacetate provides reducing equivalents to the mitochondria
through the malate-aspartate redox shuttle. During anaerobic conditions,
where a buildup of excess of reducing equivalents inhibits glycolysis, malic
acid's simultaneous reduction to succinate and oxidation to oxaloacetate
is capable of removing the accumulating reducing equivalents. This allows
malic acid to reverse hypoxia's inhibition of glycolysis and energy production.
This may allow malic acid to improve energy production in FM, reversing the
negative effect of the relative hypoxia that has been found in these patients.
Because of its obvious relationship to energy depletion during
exercise, malic acid may be of benefit to healthy individuals interested
in maximizing their energy production, as well as those with FM. In the rat
it has been found that only tissue malate is depleted following exhaustive
physical activity. Other key metabolites from the citric acid cycle needed
for energy production were found to be unchanged. Because of this, a deficiency
of malic acid has been hypothesized to be a major cause of physical exhaustion.
The administration of malic acid to rats has been shown to elevate mitochondrial
malate and increase mitochondrial respiration and energy production.
Surprisingly, relatively small amounts of exogenous malic acid were required
to increase mitochondrial energy production and ATP formation. Under hypoxic
conditions there is an increased demand and utilization of malic acid, and
this demand is normally met by increasing the synthesis of malic acid through
gluconeogenesis and muscle protein breakdown. This ultimately results in
muscle breakdown and damage. In a study on the effect of the
oral administration of malic acid to rats, a significant increase in anaerobic
endurance was found. Interestingly, the improvement in endurance was not
accompanied by an increase in carbohydrate and oxygen utilization, suggesting
that malic acid has carbohydrate and oxygen-sparing effects. In addition,
malic acid is the only metabolite of the citric acid cycle positively correlated
with physical activity. It has also been demonstrated that exercise-induced
mitochondrial respiration is associated with an accumulation of malic acid.
In humans, endurance training is associated with a significant increase in
the enzymes involved with malic acid metabolism. Because of the
compelling evidence that malic acid plays a central role in energy production,
especially during hypoxic conditions, malic acid supplements have been examined
for their effects on FM. Subjective improvement in pain was observed within
48 hours of supplementation with 1200 - 2400 milligrams of malic acid, and
this improvement was lost following the discontinuation of malic acid for
48 hours. While these studies also used magnesium supplements, due to the
fact that magnesium is often low in FM patients, the rapid improvement following
malic acid, as well as the rapid deterioration after discontinuation, suggests
that malic acid is the most important component. This interesting theory
of localized hypoxia in FM, and the ability of malic acid to overcome the
block in energy production that this causes, should provide hope for those
afflicted with FM. The potential for malic acid supplements, however, reaches
much farther than FM. In light of malic acid's ability to improve animal
exercise performance, its potential for human athletes is particularly exciting.
Additionally, many hypoxia related conditions, such as respiratory
and circulatory insufficiency, are associated with deficient energy production.
Therefore, malic acid supplements may be of benefit in these conditions.
Chronic Fatigue Syndrome has also been found to be associated with FM, and
malic acid supplementation may be of use in improving energy production in
this condition as well.. Lastly, malic acid may be of use as a general supplement
aimed at ensuring an optimal level of malic acid within the cells, and thus,
maintaining an optimal level of energy production. Reference:
G.E. Abraham and J.D. Flechas, J of Nutr Medicine 1992; 3: 49-59.