Gluconolactone is a second-generation alpha hydroxy acid. It provides similar effects to glycolic acid, but offers the added benefits of gentleness and antioxidant function.


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


Enhanced barrier function


Reinforces the stratum corneum barrier by increasing its integrity and cohesion, leading to significantly lower transepidermal water loss in response to a chemical challenge.


Skin lightening


Decreases hyperpigmentation by 10-30% after 12 weeks depending on the skin type. Also improves skin sallowness but to a smaller extent than glycolic acid. Improved skin tone evenness by approximately 30% in African Americans and Hispanics/Asians, and by >10% in Caucasians.


Smoother skin


Skin roughness improved by 30% in Caucasians and by >60% in African Americans and Hispanics/Asians after 12 weeks.


Acne treatment


14% gluconolactone is as efficacious as 5% benzoyl peroxide, but with less side effects. Can be used concurrently with tretinoin.


Wrinkle treatment


Improves both wrinkles and fine lines after 12 weeks, again to a greater extent in darker skin types than in Caucasians.


Increased skin thickness


20% gluconolactone led to 7-19% rises in the thickness of the skin of 6 elderly volunteers over periods of 2-7 months.


Less oiliness


Reduced skin oiliness in African Americans, but not in Caucasians or Hispanics/Asians.


Increased skin elasticity


Use of gluconolactone products Improved skin elasticity by 10.2% after 12 weeks, lower than the 13.5% improvement seen with glycolic acid products.


Tighter skin


After 12 weeks, Improved skin laxity by close to 5% in Caucasians and >10% in Hispanics/Asians, but not for African Americans.




Inhibits oxidation and can chelate oxidation-promoting metals. May also be able to scavenge free radicals.




Prevented UV-induced elastin promoter activation in vitro. Does not increase the sensitivity of the skin to UV light, unlike glycolic acid.

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Table of contents:

1. Sources

Chemically, gluconolactone is classified as an aldonic acid, but it is often referred to as a polyhydroxy acid because it is an organic carboxylic acid with multiple hydroxyl groups attached to carbon atoms of its alicylic chain.[1] It is found in honey, wine and musts (freshly pressed grape juice),[2][3] is an important metabolite formed from glucose in the pentose phosphate pathway during the biosynthesis of ribose,[1] and can be produced commercially through the use of bacteria, particularly Gluconobacter oxydans.[4]

2. Bioavailability

Due to its larger molecular structure, gluconolactone is expected to be absorbed into the skin more gently and more gradually than traditional alpha hydroxy acids such as glycolic acid or lactic acid.[5] We were not able to find any published studies or data on the penetration of gluconolactone to substantiate this hypothesis, but gluconolactone does nevertheless seem to exert beneficial effects on the skin, as discussed below.

3. Effects on the skin

Methods for treating wrinkles using gluconolactone were patented as early as the 1990s by the founders of Neostrata, Ruey J. Yu and Eugene J. Van Scott.[6][7]

Gluconolactone is effective on both fair and darker skin types, as evidenced by the results of a study on a regimen comprising a foaming cleanser with <1% gluconolactone, a day lotion with 4% gluconolactone and a night cream with 8% gluconolactone. Subjects from 3 different ethnic groups (African American, Caucasian and Hispanic/Asian) were recruited and all achieved significant improvements in photoaging. Moreover, those in the darker-skinned groups exhibiting greater overall improvements.[5]

A double-blind and controlled study funded by Neostrata showed that 8% gluconolactone in a base cream improved the brightness of the skin as measured by colorimetry when it was applied to sites on the forearm for 4 weeks. It was suggested that this was due to the presence of a thinner and more compact stratum corneum, which better reflects light with only minimal scattering.[8]

Further, 20% gluconolactone increased the skin thickness of 6 elderly volunteers aged between 62-81 years by 7-19% over periods ranging from 2-7 months.[9]

Gluconolactone-containing products compare well with glycolic acid-containing products, according to the results of one study. The glycolic acid producs led to statistically better improvements in skin sallowness and elasticity at the end of 12 weeks, but the 2 regimens were comparable in all other parameters, and the gluconolactone regimen was much milder and better tolerated.[10]

Gluconolactone works well in combination with other antiaging agents. A test cream containing 12% gluconolactone and 1% retinyl acetate led to an increase in skin thickness and a reduction in the depth, number and spacing of fine lines and coarse wrinkles after 12 weeks of twice daily application, in addition to improving clinical grading scores of pore size, skin laxity, skin roughness, skin sallowness, skin clarity and mottled pigmentation in a blinded and controlled study. Another study evaluated the effects of a regimen comprising a cleanser with 4% gluconolactone, a skin lightener containing 5% gluconolactone, 5% lactobionic acid, 3% kojic acid, 2% hydroquinone, a day cream with 4% gluconolactone and a night cream with 15% gluconolactone. Skin elasticity as measured by pinch recoil was significantly improved after 12 weeks, as were clinical scores for fine lines, wrinkles, pore size, laxity, roughness, sallowness, mottled pigmentation and clarity. These results were supported by photography, which revealed a smoothening of the skin texture, a diminishing in the appearance of fine lines and wrinkles in the eye area, and notable improvements in both the lightening of dark spots as well as in skin clarity.[5]

Gluconolactone also appears to be effective on male skin when used together with other alpha hydroxy acids. In a prospective, uncontrolled study on 30 men with moderate to severe photodamage of the face, the subjects were provided a foaming cleanser that contained 18% glycolic acid + 2% lactobionic acid for twice-daily use, a day cream that contained 8% gluconolactone + 2% lactobionic acid for use in the morning, and a night lotion containing 15% glycolic acid for use in the evening. This regimen led to significant improvements in fine lines, pore size, skin tone evenness and firmness after 12 weeks.[11]

3.2 Antioxidant effect

Gluconolactone has demonstrated an ability to prevent the oxidation of easily oxidized test substances such as hydroquinone and anthralin in testing models, with results similar to ascorbic acid (vitamin C) and citric acid.[12] Moreover, it is capable of chelating oxidation-promoting metals as well as trap free radicals.[13]

3.3 Photoprotection

Gluconolactone's antioxidant activity is thought to be responsible for its observed effect in preventing UV radiation-induced elastin promoter activation in vitro. This should theoretically prevent solar elastosis, a major histopathologic alteration in the dermis of photoaged skin caused by the deposition of large amounts of abnormal elastic material. Importantly, unlike glycolic acid gluconolactone did not promote the formation of sunburn cells in human skin after exposure to UV radiation, indicating that it does not increase the skin's sensitivity to UV light.[13]

3.4 Improved barrier function

Gluconolactone strengthens the barrier function of the stratum corneum. In an experiment conducted by Neostrata, 8% gluconolactone in a base cream was applied twice daily to the arm for 4 weeks, following which a 5% sodium lauryl sulphate challenge patch test was performed under occlusion. After the challenge, the gluconolactone-treated sites had significantly lower transepidermal water loss, indicative of an improved barrier function, compared to site treated with the vehicle only.[8] This is probably due to the increased integrity and cohesion of the stratum corneum, attributable to decreased degradation of desmoglein-1 and an induction of the expression of desmoglein-3 in the lower stratum corneum.[14] The classic alpha hydroxy acids such as glycolic acid and lactic acid on the other hand are known to promote desquamation.[15][16] Moreover, the erythema values of gluconolactone-treated sites were also lower, signifying an increased ability to resist irritation.[8]

3.5 Acne treatment

A double-blind clinical trial on 150 patients evaluated the efficacy of 14% gluconolactone in solution (Nuvoderm lotion) compared to its vehicle and 5% benzoyl peroxide lotion, and found that both gluconolactone and benzoyl peroxide were effective in reducing the number of acne lesions, both inflamed and non-inflamed. However, gluconolactone had the advantage that it caused fewer side effects than benzoyl peroxide.[17]

Gluconolactone is compatible with topical tretinoin in treating adult facial acne. In a single-center, blinded and controlled trial, volunteers used gluconolactone-containing products including a cleanser, a day lotion and a night cream together with a 0.1% tretinoin gel. For the 27 subjects who completed the study, total acne lesion counts declined significantly from baseline after 4 weeks of treatment, and skin irritation was only minimal.[5]

3.6 Rosacea treatment

A 12-week study of 62 rosacea patients treated with a 15% azelaic acid gel showed that even though a skin care regimen including a soap-free, 4% gluconolactone facial cleanser (Neostrata Facial Cleanser) and a 10% gluconolactone moisturizing cream (Neostrata Ultra Moisturizing Face Cream) did not improve the efficacy of the gel, it was superior to a patient-selected skin care regimen in improving skin dryness, texture, smoothness and overall condition.[18]

3.7 Psoriasis treatment

A skin care cream containing a 5% blend of gluconolactone and maltobionic acid + a 15% blend of glycolic acid, lactic acid and mandelic acid (Neostrata Problem Dry Skin Cream) descaled psoriatic plaques and improved disease severity faster and better than a 6% salicylic acid cream (Salex Cream) in a randomized, double-blind, bilateral, 2-week clinical trial on 24 adults.[19][20] Another study published 2 years later conducted a similar comparison and noted that the topical alpha-hydroxy and polyhydroxy acid cream reduced scaling more quickly, but that the efficacy of both products were relatively the same after 2 weeks of treatment.[21]

4. Side Effects

Unlike the traditional alpha hydroxy acids such as glycolic acid and lactic acid that have significant irritation potential and can cause stinging or burning sensations,[10][22] gluconolactone actually helps prevent skin irritation by reinforcing the barrier function of the stratum corneum.[8][14] In fact, it has been patented as an anti-irritant in cosmetic compositions.[23]

Scientific References

  1. Green BA, Yu RJ, Van Scott EJ. Clinical and cosmeceutical uses of hydroxyacids. Clin Dermatol. (2009)
  2. Jeffrey AE, Echazarreta CM. Medical uses of honey. Rev Biomed. (1996)
  3. Barbe JC, De Revel G, Bertrand A. Gluconic acid, its lactones, and SO(2) binding phenomena in musts from botrytized grapes. J Agric Food Chem. (2002)
  4. van Balken JAM. The industrial production of gluconolactone and gluconic acid. Biotechnological Innovations in Chemical Synthesis. (1997)
  5. Grimes PE, et. al. The use of polyhydroxy acids (PHAs) in photoaged skin. Cutis. (2004)
  6. Yu RJ, Van Scott EJ. Method of treating wrinkles using gluconic acid or gluconolactone. US Patent 5574067 (1996)
  7. Yu RJ, Van Scott EJ. Method of using gluconic acid or gluconolactone for treating wrinkles. US Patent 5677340 (1997)
  8. Berardesca E, et. al. Alpha hydroxyacids modulate stratum corneum barrier function. Br J Dermatol. (1997)
  9. Yu RJ, Van Scott EJ. Alpha-hydroxyacids and carboxylic acids. J Cosmet Dermatol. (2004)
  10. Edison BL, et. al. A polyhydroxy acid skin care regimen provides antiaging effects comparable to an alpha-hydroxyacid regimen. Cutis. (2004)
  11. Draelos ZD. Anti-Aging Effects and Tolerability of High Strength Hydroxy Acids in Males with Moderate to Severe Photoaging. J Am Acad Dermatol. (2009)
  12. Green B. After 30 years … the future of hydroxyacids. J Cosmet Dermatol. (2005)
  13. Bernstein EF, et. al. The polyhydroxy acid gluconolactone protects against ultraviolet radiation in an in vitro model of cutaneous photoaging. Dermatol Surg. (2004)
  14. 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)
  15. Van Scott EJ, Yu RJ. Alpha hydroxy acids: procedures for use in clinical practice. Cutis. (1989)
  16. Kim TH, et. al. The effects of topical alpha-hydroxyacids on the normal skin barrier of hairless mice. Br J Dermatol. (2001)
  17. Hunt MJ, Barnetson RS. A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne. Australas J Dermatol. (1992)
  18. Draelos ZD, Green BA, Edison BL. An evaluation of a polyhydroxy acid skin care regimen in combination with azelaic acid 15% gel in rosacea patients. J Cosmet Dermatol. (2006)
  19. Brouda I, et. al. 20% alpha/polyhydroxy acid cream improves the symptoms of recalcitrant hyperkeratosis. J Am Acad Dermatol. (2011)
  20. Green BA, et. al. Double-blind, randomized, bilateral comparison of topical 6% salicylic acid cream and 20% alpha poly hydroxy acid cream to reduce scaling of lesions associated with moderate, chronic plaque psoriasis. J Am Acad Dermatol. (2010)
  21. Akamine KL, et. al. A double-blind, randomized clinical trial of 20% alpha/poly hydroxy acid cream to reduce scaling of lesions associated with moderate, chronic plaque psoriasis. J Drugs Dermatol. (2013)
  22. Smith WP. Comparative effectiveness of alpha-hydroxy acids on skin properties. Int J Cosmet Sci. (1996)
  23. Weinkauf R, et. al. Gluconolactones and glucarolactones as anti-irritants in cosmetic compositions. US Patent 6036963 (2000)