Malic Acid

Malic acid, an alpha-hydroxy organic acid, is sometimes referred to as a fruit acid. This is because malic acid is found in apples and other fruits. It is also found in plants and animals, including humans. In fact, malic acid, in the form of its anion malate, is a key intermediate in the major biochemical energy-producing cycle in cells known as the citric acid or Krebs cycle located in the cells' mitochondria.

Malic acid is a chiral molecule. The naturally occurring stereoisomer is the L-form. The L-form is also the biologically active one. There is some preliminary evidence that malic acid, in combination with magnesium, may be helpful for some with fibromyalgia. Malic acid sold as a supplement is mainly derived from apples and, therefore, is the L-form. Malic acid is a naturally occurring compound that plays a role in the complex process of deriving adenosine triphosphate (ATP; the energy currency that runs the body) from food. Although uncontrolled research had suggested that the combination of 1,200–2,400 mg per day of malic acid and 300–600 mg of magnesium for eight weeks reduced symptoms of fibromyalgia,1 double-blind evidence has shown that malic acid plus magnesium fails to help people with this condition.

Malic acid is absorbed from the gastrointestinal tract from whence it is transported via the portal circulation to the liver. There are a few enzymes that metabolize malic acid. Malic enzyme catalyzes the oxidative decarboxylation of L-malate to pyruvate with concomitant reduction of the cofactor NAD+ (oxidized form of nicotinamide adenine dinucleotide) or NADP+ (oxidized form of nicotinamide adenine dinucleotide phosphate). These reactions require the divalent cations magnesium or manganese. Three isoforms of malic enzyme have been identified in mammals: a cytosolic NADP+-dependent malic enzyme, a mitochondrial NADP+-dependent malic enzyme and a mitochondrial NAD(P)+-dependent malic enzyme. The latter can use either NAD+ or NADP+ as the cofactor but prefers NAD+. Pyruvate formed from malate can itself be metabolized in a number of ways, including metabolism via a number of metabolic steps to glucose. Malate can also be metabolized to oxaloacetate via the citric acid cycle. The mitochondrial malic enzyme, particularly in brain cells, may play a key role in the pyruvate recycling pathway, which utilizes dicarboxylic acids and substrates, such as glutamine, to provide pyruvate to maintain the citric acid cycle activity when glucose and lactate are low.

Malic acid is also a natural constituent of many fruits and vegetables that are preserved by fermentation. This acid may be broken down during fermentation by certain bacteria into lactic acid and carbon dioxide. This reaction is desired to reduce the acidity in certain types of wines, and is undesired in the fermentation of cucumbers because of gaseous spoilage from carbon dioxide accumulation inside the fruit.

Many traditional fresh and fermented ready-to-eat foods are dependent on their acidity as the primary means for controlling the presence of disease- causing bacteria. In such foods, how quickly pathogenic microorganisms are inactivated is dependent on both the level of acidity (pH) and the identity and amount of the specific acid associated with the food. Recent concern about the survival of acid resistant pathogens in apple cider produced a need for better information on how malic acid, the principal acid in apples, affects bacteria. The current study helps address that need by providing information on how malic acid and pH interact to inactivate the foodborne pathogen, Listeria monocytogenes. These results demonstrate that malic acid is one of the gentler food acids.

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 Primary fibromyalgia (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.

CAS Number: 6915-15-7
Chemical Formula: C4H6O5