Lactobionic Acid

Lactobionic acid is derived from the milk sugar lactose. It has several beneficial properties that can form the basis for desirable cosmetic claims, including its antioxidant function, lightening and moisturizing effects.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

C

Increased skin hydration

Mild

Has strong water-binding properties and has demonstrated the ability to increase the production of glycosaminoglycans in the skin.

D

Enhanced barrier function

Moderate

Increases the integrity and cohesion of the stratum corneum and accelerates barrier recovery.

D

Skin lightening

Mild

Suppresses melanin production in cultured mouse melanocytes in the presence of an analog of a melanocyte stimulating hormone. The effect was weaker than that of kojic acid.

D

Increased skin thickness

Mild

8% lactobionic acid increased skin thickness of the forearm by an average of 6.9% after 12 weeks, compared to a 1.9% increase in untreated forearms.

D

Antioxidant

Mild

Scavenges free radicals and inhibits lipid peroxidation. Significantly weaker antioxidant activity compared to α-tocopherol.

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Scientific Research


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Table of contents:

1. Sources

Lactobionic acid is an aldobionic acid comprising one molecule of the sugar galactose and one molecule of gluconic acid attached via an acetal linkage.[1] It is also often referred to as a polyhydroxy bionic acid due to its multiple hydroxyl groups.

Lactobionic acid is derived from the oxidation of lactose, the main milk sugar,[2] and it has also been detected in yogurt.[3] It is produced industrially through the use of microbes or via a biocatalytic approach,[4] and has many applications in food, pharmaceuticals, medicine and cosmetics.[5][6]

2. Bioavailability

Lactobionic acid has a molar mass of 358 daltons and is a larger molecule than traditional alpha hydroxy acids. It has been asserted that lactobionic acid is still small enough to penetrate the skin,[2] but no permeation data have been published to date.

3. Effects on the skin

3.1 Effect on skin hydration

Lactobionic acid is considered highly hygroscopic, with the ability to attract and retain water better than the humectants glycerin and sorbitol.[1] However, its potential to hydrate the skin may or may not be realized depending on the formulation. Alkyl polyglucoside emulsions containing 6% or 10% lactobionic acid did not significantly improve skin moisture compared to the emulsion alone, for instance.[7][8] Because the emulsion itself has large numbers of hydroxyl groups and the potential for sustained skin hydration, it has been suggested that the interaction between it and lactobionic acid decreased the expected beneficial effect of lactobionic acid.[9]

However, application of an 8% lactobionic acid cream to the forearm 3 times a day for 12 weeks did lead to an increase in water-binding glycosaminoglycans according to histologic analysis.[10] 6% lactic acid in gel and emulsion formulations also increased skin hydration as measured by electrical capacitance.[7]

3.2 Lightening effect

Lactobionic acid has been demonstrated to inhibit melanin synthesis in cultured mouse melanocytes in the presence of an analog of α-melanocyte stimulating hormone. Though the effect was smaller compared to that of kojic acid, this result suggests that lactobionic acid may have the capacity to block melanocyte activity and suppress melanin production induced by an exogenous source, such as UV radiation, and hence reduce the potential for hyperpigmentation and irregular pigmentation of sun-exposed skin.[11]

6% lactobionic acid in a alkylpolyglucoside-based emulsion led to a marked decrease in the melanin index after being applied to skin sites on the forearm for only 2 weeks, further demonstrating its lightening effect.[7] Since lactobionic acid has been found to increase exfoliation or cell turnover, this has been hypothesized to be another factor responsible for lactobionic acid's observed whitening effect.[7][12]

A few manufacturer-sponsored studies have evaluated the antiaging effects of lactobionic acid. In one, 33 women applied a formulation of 8% lactobionic acid in a cream base to the entire face twice daily and to one outer forearm thrice daily, leaving the other forearm untreated. Visual grading of the face showed significant improvements in all parameters (fine lines, coarse wrinkles, pore size, laxity, sallowness, roughness, clarity and mottled hyperpigmentation) within 6 weeks, and skin elasticity as measured by pinch recoil increased by 14.5% after 12 weeks. However, since the women were allowed to use their regular beauty products in conjunction with the test cream throughout the study, it is not possible to conclude that the lactobionic acid formulation led to these improvements. Biopsy specimens taken from the forearms of 16 of the women did show a significant (6.9%) increase in skin thickness relative to baseline in treated forearms that was more than the increase observed for the untreated forearms (1.9%), due to an increase in viable epidermal thickness and dermal glycosaminoglycans, which builds volume in the skin.[10] This effect was confirmed in a separate experiment on 7 elderly volunteers aged 49-76 years. 1 obtained a 26% increase in skin thickess after applying 8% lactobionic acid for 3 months, 2 achieved 5% and 12% increases in thickness after 4-5 months of using 10% lactobionic acid, and the remaining 4 saw increases ranging from 10-58% after applying 20-22% lactobionic acid for 4-10 months.[13]

Another study focused on the effects of a topical regimen containing high strength glycolic acid combined with gluconolactone and lactobionic acid on male skin. 30 men were recruited and provided with the following products: a foaming cleanser containing 18% glycolic acid + 2% lactobionic acid for use twice daily, a day cream containing 8% gluconolactone + 2% lactobionic acid for use every morning and a night lotion containing 15% glycolic acid for use every evening. After 12 weeks, fine lines, pore size, evenness of skin tone and skin firmness were all significantly improved,[14] but again it was not possible to pinpoint the effects of lactobionic acid.

In vitro experiments have revealed that lactobionic acid inhibits the activity of matrix metalloproteinases, including matrix metalloproteinase-9 and Clostridium Collagenase IV. It therefore has the ability to block collagen degradation, which can help preserve the dermal matrix in aging skin.[10][14][15] Lactobionic acid has also been shown to increase mucopolysaccharides, representing an increase in water-binding glycosaminoglycans which can plump and firm the skin.[10]

3.4 Antioxidant effect

Lactobionic acid possesses the ability to chelate iron, a property that allows it to completely repress the production of hydroxyl radicals and which accounts for its effectiveness as an organ preservant.[16][17][18]

α-tocopherol was substantially better than lactobionic acid in 2 assays on free radical scavenging activity and lipid peroxidation.[9]

3.5 Improved barrier function

Acidification of the stratum corneum by topical application of lactobionic acid has been shown to accelerate barrier recovery in moderately aged mouse epidermis[19] and type I-II human skin.[20] This is attributable to an enhanced lipid processing by 2 key enzymes with acidic pH optima, thereby increasing the rate of formation of mature lamellar bilayers. In addition, the degradation of desmoglein-1 is inhibited and the expression desmoglein-3 in the lower stratum corneum is induced, leading to an improved stratum corneum integrity and cohesion.[21]

Topical lactobionic acid also substantially prevented the emergence of the macroscopic and functional abnormalities in an atopic-like dermatitis induced in mouse skin by repeated challenges with the chemical allergen oxazolone.[22]

4. Side Effects

Although lactobionic acid has not yet been evaluated for its overall safety when used in cosmetics, 6% lactobionic acid preparations were well-tolerated in one study, neither irritating the skin nor producing skin barrier impairment.[7] In vitro, 0.25% and 2.5% lactobionic acid showed acceptable cell viability. 25% lactobionic acid led to an unacceptable decline in cell viability to less than 50%, but this concentration was not considered reflective of actual applications.[8]

Scientific References


  1. Draelos ZD. PHAs and bionic acids: next generation hydroxy acids. Procedures in Cosmetic Dermatology Series: Cosmeceuticals. (2009)
  2. Green BA, Yu RJ, Van Scott EJ. Clinical and cosmeceutical uses of hydroxyacids. Clin Dermatol. (2009)
  3. Kiryu T, et. al. Involvement of Acetobacter orientalis in the production of lactobionic acid in Caucasian yogurt ("Caspian Sea yogurt") in Japan. J Dairy Sci. (2009)
  4. Alonso S, Rendueles M, Díaz M. Bio-production of lactobionic acid: current status, applications and future prospects. Biotechnol Adv. (2013)
  5. Gutiérrez LF, Hamoudi S, Belkacemi K. Lactobionic acid: A high value-added lactose derivative for food and pharmaceutical applications. Int Dairy J. (2012)
  6. Alonso S, Rendueles M, Díaz M. Efficient lactobionic acid production from whey by Pseudomonas taetrolens under pH-shift conditions. Bioresour Technol. (2011)
  7. Tasic-Kostov M, et. al. Lactobionic acid in a natural alkylpolyglucoside-based vehicle: assessing safety and efficacy aspects in comparison to glycolic acid. J Cosmet Dermatol. (2010)
  8. Tasic-Kostov MZ, et. al. Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems? Pharmazie. (2011)
  9. Tasic-Kostov M, et. al. Lactobionic acid as antioxidant and moisturizing active in alkyl polyglucoside-based topical emulsions: the colloidal structure, stability and efficacy evaluation. Int J Cosmet Sci. (2012)
  10. Green BA, Edison BL, Sigler ML. Antiaging Effects of Topical Lactobionic Acid: Results of a Controlled Usage Study. Cosmet Dermatol. (2008)
  11. Brouda I, et. al. Lactobionic Acid Anti-Aging Mechanisms: Antioxidant Activity, MMP Inhibition, and Reduction of Melanogenesis. J Am Acad Dermatol. (2010)
  12. Green BA. Cosmeceutical Uses and Benefits of Alpha, Poly and Bionic Hydroxy Acids. Cosmeceuticals and Cosmetic Practice. (2014)
  13. Yu RJ, Van Scott EJ. Alpha-hydroxyacids and carboxylic acids. J Cosmet Dermatol. (2004)
  14. Draelos ZD. Anti-Aging Effects and Tolerability of High Strength Hydroxy Acids in Males with Moderate to Severe Photoaging. J Am Acad Dermatol. (2009)
  15. Upadhya GA, Strasberg SM. Glutathione, lactobionate, and histidine: cryptic inhibitors of matrix metalloproteinases contained in University of Wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions. Hepatology. (2000)
  16. Charloux C, et. al. Inhibition of hydroxyl radical production by lactobionate, adenine, and tempol. Free Radic Biol Med. (1995)
  17. Isaacson Y, et. al. Lactobionic acid as an iron chelator: a rationale for its effectiveness as an organ preservant. Life Sci. (1989)
  18. Shepherd RE, et. al. Lactobionic and gluconic acid complexes of FeII and FeIII; control of oxidation pathways by an organ transplantation preservant. J Inorg Biochem. (1993)
  19. Choi EH, et. al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol. (2007)
  20. Gunathilake R, et. al. pH-regulated mechanisms account for pigment-type differences in epidermal barrier function. J Invest Dermatol. (2009)
  21. Hachem JP, et. al. Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes. J Invest Dermatol. (2010)
  22. Hatano Y, et. al. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Invest Dermatol. (2009)