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Malic acid

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malic acid
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What is malic acid
Malic acid vs Citric acid
Citric acid uses
Malic acid foods
Malic acid uses
Malic acid side effects

What is malic acid

Malic acid (2-hydroxybutanedioic acid) is a tart-tasting organic dicarboxylic acid that plays a role in many sour or tart foods. Malic acid is an important commercial chemical used in canning fruits and vegetables to prevent them from spoiling. Malic acidis used predominantly in the food and beverage industries as an acidulant and taste enhancer/modifier, particularly in combination with artificial sweeteners 1. Additionally, the U.S. Department of Energy has identified malic acid as a building block chemical that can be converted to various high-volume chemical products from renewable sources of carbohydrate and converted to various chemical products 2. Malic acid is used in various other foods, dry beverage powders, carbonated beverages, and food packaging materials to control acidity. Malic acid is an ingredient in some household cleaners, hair coloring, nail enamels, human and specialty pet shampoos. The future use of malic acid is predicted to be over 200,000 tons per year 3.

Malic acid is an intermediate in the tricarboxylic acid cycle, also known as the citric acid or Krebs cycle, which is essential for the oxidative metabolism of carbohydrates and the production of adenosine triphosphate (ATP) 4. Malic acid is formed from fumaric acid and is oxidized to oxaloacetic acid. Malic acid is also metabolized to pyruvic acid by malic enzyme which is present in many biologic systems, including bacteria and plants. L-Malic and DL-malic acid are both rapidly metabolized in the rat. The L‐isoform of malic acid occurs naturally in apples and many other fruits and plants 5. Orally or intraperitoneally administered l- or dl-malic acid was extensively eliminated as carbon dioxide (83 to 92%). No differences between the two forms were found in the rates (90 to 95% in 24 hour) or routes of excretion. Both enantiomers of malic acid are readily metabolised by laboratory animals and humans and that there was no reason to distinguish between L-malic acid and DL-malic acid when considering their safe use in food 6.

Both the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1980) and the SCF (1991) concluded that there was clear evidence that both enantiomers of malic acid are readily metabolised by laboratory animals and humans and that there was no reason to distinguish between l‐malic acid and dl‐malic acid when considering their safe use in food.

Malic acid pH: a 0.001% aqueous malic acid solution pH is 3.80, that of 0.1% malic acid solution pH is 2.80, and that of a 1.0% malic acid solution  pH is 2.34.

Malic acid and its salts are considered as strongly irritant to the skin and mucosa and as a particular risk to the eyes. Exposure via inhalation for those handling the additives is also considered to present a risk. Severe skin and eye irritation can occur with direct contact to malic acid or its salts. Allergic skin reactions have been reported in some individuals after eating foods containing malic acid. Erosion of tooth enamel may occur from drinking acidic soft drinks containing malic acid. Weakness, incoordination, convulsions, and breathing difficulties occurred in laboratory animals given very high oral doses of malic acid. Death occurred in some animals. No health problems occurred in laboratory animals, dogs, or cattle fed low-to-moderate doses over time. Malic acid did not cause birth defects or reproductive effects in laboratory animals. The potential for malic acid to cause cancer has not been assessed in laboratory animals. The potential for malic acid to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, the U.S. National Toxicology Program 13th Report on Carcinogens, or the California Office of Environmental Health Hazard Assessment.

Malic acid vs Citric acid

Citric acid (2-hydroxy-1,2,3-propane-tricarboxylic acid) is a weak organic acid found in the greatest amounts in citrus fruits, such as lemon, lime, grapefruit, tangerine, and orange 7. Lemon and lime juices are rich sources of citric acid, containing 1.44 and 1.38 g/oz, respectively, comprising as much as 8% of the dry fruit weight 8. The citric acid content of commercially available lemonade and other juice products varies widely, ranging from 0.03 to 0.22 g/oz. Citric acid is frequently used as a food additive as a natural preservative and also to add an acidic (sour) taste to foods and beverages 9. Citric acid is also a key intermediate in cellular metabolism, being a component of the tricarboxylic acid or Krebs cycle, citric acid is found in all human and animal tissues as an intermediary substance in oxidative metabolism. A major source of citric acid in your body results from endogenous metabolism in the mitochondria via the production of ATP in the citric acid cycle (see Citric acid cycle below).

Citric acid molar mass is 192.027 g/mol (anhydrous) and 210.14 g/mol (monohydrate) 10.

Citric acid occurs in all living organisms as an intermediate substance in oxidative metabolism in the tricarboxylic acid or Krebs cycle. A major source of citric acid in your body results from endogenous metabolism in the mitochondria via the production of ATP in the citric acid cycle (see Citric acid cycle below). Citric acid is a natural component of fruit, vegetables and plants (roots and leaves). Citric acid is found in significant quantities in lemon and lime juices (41 and 39 mg/kg for ready-to-consume juice and 31 and 30 mg/kg for concentrates, respectively). Levels of citric acid in commercial lemon juice-baseddrinks, such as lemonade, fall in the range of 0.62 to 0.96 mg/kg. Other dietary sources of citric acid include grapefruits and oranges (significant levels), berries and beans.

Citric acid (E330, anhydrous and monohydrate) is approved as a food additive 11 for general use in foodstuffs following the quantum satis principle (limits set for some food products, i.e. juices, infantfoods). It has a long history of use as an additive in food 12, cosmetics 13, pharmaceuticals (human and veterinary), plant protection products, biocides 14 and household cleaning products.
Citric acid has been assessed by the Joint FAO/WHO (Food and Agriculture Organization/World Health Organization) Experts Committee on Food Additives 13. The Committee allocated an acceptable daily intake (ADI) of ‘not limited’ for citric acid and its calcium, potassium and sodium salts. This position was retained by the Scientific Committee on Food (SCF) 15.

Furthermore, both the European Food Safety Authority (EFSA) 16, 17, 18 and U.S. Food and Drug Administration (FDA) has granted citric acid GRAS status (Generally Recognized as Safe) as an antioxidant, emulsifier, stabilizer and thickener in infant formula 19 and as an emulsifier in combination with lauramide ethyl ester in food in general, including meat and poultry 20.

Citric acid uses

Functional uses of citric acid as synergist for antioxidants, sequestrant, acidity regulator and flavoring agent 21. Citric acid is a preservative that more effective than acetic and lactic acids at inhibiting the growth of thermophilic bacteria 22. Citric acid is widely used in carbonated drinks and as an acidifier (reduce pH) of foods. It is less effective at controlling the growth of yeasts and mold than the other acids.

Citric acid (anhydrous and monohydrate) is approved as a food additive for use as a preservative in a wide range of commonly consumed foods and is authorized as a preservative in feed for all animal species without restrictions 23. “Citric acid is a normal constituent of the diet of humans and animals and, when ingested, is rapidly and completely metabolised to carbon dioxide and water; therefore, the use of citric acid in animal nutrition would not pose a risk to the environment”23.

Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. Citrate salts of various metals are used to deliver minerals in biologically-available forms; examples include dietary supplements and medications. It maintains stability of active ingredients and is used as a preservative. Citric acid is also used as an acidulant to control pH.

Gastrointestinal absorption of citric acid from dietary sources has been associated with a modest increase in urinary citrate excretion 24. The salts of citric acid (citrates) or anhydrous citric acid can be used as anticoagulants due to their calcium chelating ability in blood and as calcium kidney stones dissolution agent. The mechanism of action of anhydrous citric acid in calcium kidney stones dissolution agent is its acidifying activity and calcium chelating activity. Furthermore, knowledge of the citric acid content of beverages may be useful in nutrition therapy for calcium urolithiasis (formation of calcium kidney stones), especially among patients with hypocitraturia 25. Citrate is a naturally-occurring inhibitor of urinary crystallization; achieving therapeutic urinary citrate concentration is one clinical target in the medical management of calcium urolithiasis. When provided as fluids, beverages containing citric acid add to the total volume of urine, reducing its saturation of calcium and other crystals, and may enhance urinary citrate excretion.

Urinary citrate is a potent, naturally-occurring inhibitor of urinary crystallization 25. Citrate is freely filtered in the proximal tubule of the kidney. Approximately 10% to 35% of urinary citrate is excreted; the remainder is absorbed in various ways, depending on urine pH and other intra-renal factors. Citrate is the most abundant organic ion found in urine. Hypocitraturia, defined as <320 mg (1.67 mmol) urinary citrate/day 26, is a major risk factor for calcium urolithiasis. The activity of citrate is thought to be related to its concentration in urine, where it exhibits a dual action, opposing crystal formation by both thermodynamic and kinetic mechanisms. Citrate retards stone formation by inhibiting the calcium oxalate nucleation process and the growth of both calcium oxalate and calcium phosphate stones, largely by its ability to bind with urinary calcium and reduce the free calcium concentration, thereby reducing the supersaturation of urine. Citrate binds to the calcium oxalate crystal surface, inhibiting crystal growth and aggregation 27. There is also evidence that citrate blocks the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells 28. Medical interventions to increase urinary citrate are a primary focus in the medical management of urolithiasis 29. The amount of diet-derived citrate that may escape in body conversion to bicarbonate is reportedly minor 30. Nonetheless, a prior study reported increased urinary citrate after 1 week on 4 ounces lemon juice per day, diluted in 2 L water, in stone formers with hypocitraturia 24. Two retrospective studies showed an effect in calcium stone formers of lemon juice and/or lemonade consumption on urinary citrate 31, but a recent clinical trial showed no influence of lemonade on urinary citrate 32.

Studies indicated that citrate decreases lipid peroxidation and downregulates inflammation by reducing polymorphonuclear cell degranulation and attenuating the release of myeloperoxidase, elastase, interleukin (IL)-1β, and platelet factor 4 33. In test tube study, citrate improved endothelial function by reducing the inflammatory markers and decreasing neutrophil diapedesis in hyperglycemia 34. Moreover, citric acid has been shown to reduce hepatocellular injury evoked in rats by carbon tetrachloride 35. Citric acid might thus prove of value in decreasing oxidative stress. Another animal study in mice 7 suggests an antioxidant and anti-inflammatory effect for orally given citric acid at 1–2 g/kg in brain tissue, but this protective effect is lost when the dose is increased to 4 g/kg. Citric acid also demonstrated a beneficial hepatic protective effect at this dose range. Given that both increased brain oxidative stress and chronic inflammation have been linked to the development of neurodegenerative diseases, citric acid might thus prove of clinical benefit in such conditions.

Malic acid foods

The food that is most well known for its high malic acid content is the apple. Other fruits with a very high concentration of malic acid are apricot, mango, rose, plum, elderberry, buckwheat, strawberry, pineapple, papaya, orange, tangerine, potato, grape, soybean, grapefruit, lettuce, onion, celery, oats, cauliflower, cabbage, brussel sprouts, tobacco, carrot, olive, sunflower, tomato, ginseng, opium poppy, pea, raspberry, sage, and corn 36.

Reported food use categories for malic acid include baked goods, frozen dairy, nonalcoholic beverages and soft candy 37. Malic acid occurs in maple sap, melon, papaya, beer, grape wine, cocoa, sake, kiwifruit and chicory root 37.

Malic acid contributes to the sourness of green (unripe) apples. Malic acid is present in grapes and in most wines with concentrations sometimes as high as 5 g/l 38. It confers a tart taste to wine, although the amount decreases with increasing fruit ripeness. The taste of malic acid is very clear and pure in rhubarb, a plant for which it is the primary flavor. It is also a component of some artificial vinegar flavors, such as “salt and vinegar” flavored potato chips.

Malic acid is also used as a flavor enhancer for many drinks and candies. It is especially common in diet sodas and other artificially sweetened drinks. This is also true of artificially sweetened candies, such as gum and other gummy candies. Because of its highly versatile nature, especially in masking unnatural flavors, it has become an important part of nearly any food product that contains alternative sweeteners.

Table 1. The top forty plants containing malic acid

Common name Part Concentration (ppm)
Indian SorrelFlower; Leaf; Stem65,000; 12,500; 6,000
DogbrierFruit62200
Rowan berryFruit39000
MangoFruit36600
FigFruit; Leaf30,200; 23,400
ApricotFruit22000
European ElderberryFruit19000
BuckwheatLeaf15100
PlumFruit15000
TamarindLeaf; Fruit15,000; 10,000
BuckthornFruit15,000-29,000
StrawberryFruit8000
GooseberryFruit7300
Pot-MarigoldFlower6400
GenipapFruit6300
Star FruitFruit1-12,100
PurslanePlant5100
PineappleFruit4700
PapayaLatex exudate4400
BananaFruit3730
Red CurrantFruit2600
JimsonweedPlant2120
TangerineFruit2100
LimeFruit2000
OrangeFruit2000
European GrapeFruit2000
PassionfruitFruit1,200-3,800
Prickly PearFruit1700
TomatilloFruit1500
PotatoTuber1120
CalamansiFruit Juice0-2,000
SoybeanSeed1000
GrapefruitFruit600
LettuceLeaf600

ppm = parts per million

[Source 39]

Malic acid uses

Malic acid, a sort of alpha-hydroxy acids (AHAs) found in fruits and many vegetables, has been commonly used in cosmetics and chemical peeling agents 40. Over 50 cosmetic formulations across a range of products have contained malic acid 41. Malic acid functions in cosmetic formulations as a pH adjuster and sodium malate functions as a skin conditioning agent-humectant. Malic acid is used for light-damaged or dry skin, and acne 42. The exact biological and molecular mechanisms of malic acid in human epidermal keratinocytes still remain unclear. Furthermore, safety concerns of the adverse reactions of alpha-hydroxy acids (AHAs) including redness, swelling, burning, pruritus, phototoxicity, and facial hyperkeratosis were pronounced 43. Malic acid may induce skin and ocular irritation 41.

Malic has been used as salivary stimulants in xerostomia (dry mouth sensation), but its use has been discontinued because of malic acid demineralizing effect
44. Several studies have demonstrated that 1% malic acid, in combination with xylitol and fluoride, exerts no or little effect on tooth demineralization and maintains its properties as a salivary stimulant 45. In fact, recent studies have demonstrated promissory results of 1% malic acid; they have reported an increase in salivary flow and a reduction in dry mouth sensation 46. Malic acid stimulates salivary flow by dissociating into H+ ions when mixed with water and becoming hydronium ions (H3O+), leading to saliva secretion to neutralize the acid formation 47. Recently, a new spray formulation containing 1% malic acid, 10% xylitol, and 0.05% fluoride (Xeros Dentaid Spray) has been proven to be clinically safe and efficient in reducing xerostomia and increasing salivary flow rates in patients with dry mouth secondary to drugs 48.

Malic acid is an indirect food additive for use only as a component of adhesives.

Malic acid used as a general purpose food additive in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice. Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe (GRAS) for their intended use.

There is only one study (24 participants) conducted 1995 using malic acid, Super Malic, a proprietary tablet containing malic acid (200 mg) and magnesium (50 mg) for fibromyalgia 49. However, no clear treatment effect attributable to Super Malic was seen in the blinded, fixed low dose trial.

In in vivo rat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation 50. In test tube experiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury 50. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects 50.

Malic acid side effects

Malic acid and its salts are considered as strongly irritant to the skin and mucosa and as a particular risk to the eyes. Exposure via inhalation for those handling the additives is also considered to present a risk. Severe skin and eye irritation can occur with direct contact to malic acid or its salts. Allergic skin reactions have been reported in some individuals after eating foods containing malic acid. Erosion of tooth enamel may occur from drinking acidic soft drinks containing malic acid. Weakness, incoordination, convulsions, and breathing difficulties occurred in laboratory animals given very high oral doses of malic acid. Death occurred in some animals. No health problems occurred in laboratory animals, dogs, or cattle fed low-to-moderate doses over time. Malic acid did not cause birth defects or reproductive effects in laboratory animals. The potential for malic acid to cause cancer has not been assessed in laboratory animals. The potential for malic acid to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, the U.S. National Toxicology Program 13th Report on Carcinogens, or the California Office of Environmental Health Hazard Assessment.

An efficacy and safety test of a tablet containing 200 mg malic acid (and 50 mg magnesium) was conducted using patients with primary fibromyalgia syndrome 51. In the first part of the test, 24 patients were given three tablets twice daily for 4 weeks. In the second part, 16 patients started with three tablets bid and increased the dosage every 3 to 5 days as necessary; at month 6, the average dose was 8.8 tablets per day. (For a 50-kg person, ingestion of six tablets would be equivalent to 24 mg of malate/kg of body weight). In the first part of the study, one test patient reported diarrhea, one reported nausea, and one reported dyspepsia. In the placebo group, two patients reported diarrhea and one reported dyspepsia. In the second part of the study, five test patients reported diarrhea, one reported nausea, one reported dyspepsia, one reported panic attacks, and one reported dizziness.

Thirty-four patients with atopic dermatitis were tested to determine their sensitivity to foods containing malic (and citric) acid 51. The patients were first patch tested with malic (and citric) acid applied as a 10% aqueous solution under occlusive patches for 48 hours. For 2 weeks, the patients followed a diet that avoided processed foods in which malic (and citric) acid were used, and then challenged themselves with a diet high in malic (and citric) acid the during the third week. Eighteen patients reacted to both malic and citric acid and 6 patients reacted to only malic acid. Both immediate reactions (seasonal allergic rhinitis and urticaria) and delayed reactions (contact dermatitis) were present. Patch-test results were reliable in predicting results of the challenge with diet 51.

The subjective skin irritation potential of malic acid was evaluated by applying 2 mg/cm² of 1 M malic acid in vehicle (15% ethanol [SD40], 5% ethoxydiglycol, and 5% butylene glycol) to the nasal fold area of at least 10 subjects. Irritation was graded on a scale of 0 to 4 every minute for 15 minutes. The irritation scores, as an average of the summation of each individual irritation score over the 15-minute test period, were 39.4, 37.1, and 23.1 for pH 3, 5, and 7, respectively 51.

The consumption of malic acid and acidic soft drinks may lead to demineralization and softening of human dental enamel, known as dental erosion 52.

Malic acid was relatively nontoxic in acute toxicity studies using animals. In a chronic oral study, feeding malic acid to rats resulted only in weight gain changes and changes in feed consumption. Malic acid did not cause reproductive toxicity in mice, rats, or rabbits. Malic acid was a moderate to strong skin irritatant in animal tests, and was a strong ocular irritant. Malic acid was not mutagenic across a range of genotoxicity tests.

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