Malic Acid, Energy, &
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 FMs 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 (Krebs) 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 acids simultaneous reduction to succinate and
oxidation to oxaloacetate is capable of removing the accumulating reducing
equivalents. This allows malic acid to reverse hypoxias 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
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
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 acids 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
source of nutrients and supplements.
did we qualify them ?
G.E. Abraham and J.D. Flechas, J of Nutr Medicine 1992; 3: 49-59.
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