Malic Acid and Magnesium in Fibro

DESCRIPTION

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, also known as apple acid, hydroxybutanedioic acid and hydroxysuccinic 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. L-malic acid has the following chemical structure:

L-malic Acid
ACTIONS AND PHARMACOLOGY
ACTIONS

Malic acid, in combination with magnesium, has putative antifibromyalgic activity.
MECHANISM OF ACTION

The mechanism of malic acid's putative antifibromyalgic activity is unknown.
PHARMACOKINETICS

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.

Clearly, the metabolism of malic acid is complex and what any of the above has to do, if anything, with malic acids' putative activity in those with fibromyalgia is entirely unclear.
INDICATIONS AND USAGE

Malic acid may help some with fibromyalgia.
RESEARCH SUMMARY

Results have been mixed in studies of malic acid's possible effects in those with fibromyalgia. In a double-blind, placebo-controlled crossover study, subjects with primary fibromyalgia syndrome were randomized to receive a combination of 200 milligrams of malic acid and 50 milligrams of magnesium per tablet (three tablets twice a day) or placebo for four weeks. This was followed by a six-month, open-label trial with dose escalating up to six tablets twice a day. Outcome variables were measures of pain and tenderness, as well as functional and psychological measures.

No clear benefit was observed for the malic acid/magnesium combination in the lower-dose blinded trial. But in the open-label trial, at higher doses, there were significant reductions in the severity of all three primary pain/tenderness measures. Follow-up is needed.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
CONTRAINDICATIONS

None known for malic acid. See Magnesium.
PRECAUTIONS

Because of lack of long-term safety studies, supplementary malic acid should be avoided by pregnant women and lactating mothers. See Magnesium.
INTERACTIONS

None reported for malic acid. See Magnesium.
DOSAGE AND ADMINISTRATION

The doses used in the fibromyalgia studies were L-malic acid, 1200 to 2400 milligrams daily, and magnesium, 300 to 600 milligrams daily.
HOW SUPPLIED

Tablets — 350 mg
LITERATURE

Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double-blind, placebo-controlled pilot study. J Rheumatol. 1995; 22:953-958.

Young Z, Floyd DL, Loeber G, Tong L. Structure of a closed form of human malic enzyme and implications for catalytic mechanism. Nature Struct Biol. 2000; 7:251-257.