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pH Buffering Considerations in Mature Skin*

Contact Author Howard I. Maibach, MD, University of California School of Medicine; and Jackie Levin, MD, Largo Medical Center
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The acidic character of skin’s outer surface was first described in 1892 by Heuss1 and years later by Schade and Marchionini2 as acid mantle, and its importance has been recognized as playing a crucial role in permeability barrier homeostasis, skin integrity/cohesion and immune function.3–5 Given the significance of an acidic skin pH for normal functioning and defenses, it is important that the skin is therefore able to resist acidic/alkaline aggression to some extent—i.e., has a buffering capacity.6 With age, however, the pH of skin increases and its ability to buffer this change in pH decreases,7 which results in impaired barrier homeostasis and skin integrity/cohesion, an increased likelihood for skin infection, and increased sensitivity/irritation to topically applied products.8

This paper briefly reviews the basic science of pH and buffering capacity and the deleterious effects of increased pH in mature skin. In more detail, the authors consider which components of the stratum corneum (SC) are likely responsible for buffering capacity in skin of all ages, and discuss physiologic changes in the SC that may contribute to the decreased buffering capacity detected in mature skin.

pH and Buffering Capacity

pH is a measure of the hydronium ion concentration in the skin. When dilute aqueous acid or alkaline solutions come into contact with healthy skin, the pH changes—although this is generally temporary and the original pH is rapidly restored via buffering. Recall that a buffer is a chemical system that can limit changes in pH when an acid or a base is added.

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Buffer solutions consist of a weak acid and its conjugated base and exhibit optimum buffering capacity when approximately 50% of it is dissociated, i.e., at a pH about equal to its pKa.6, 9 The pKa is the negative of the common logarithm of the acid dissociation constant (Ka) and is a measure for the strength of the acid. The buffer capacity is further dependent upon the concentration of the system. An acid/alkali aggression test is one way to measure the acid/alkali resistance or buffering capacity of the skin. Such tests commonly were used in the 1960s to detect the likelihood of workers in certain chemical work environments to develop occupational diseases.6 A mild variation of the alkali/acidic resistance tests, also called acid/alkali neutralization tests, assesses how quickly the skin is able to buffer applied acids/bases without the occurrence of skin corrosion. Repetitive applications of acid or base demonstrate that the skin’s buffering capacity is limited and may be overcome, which is illustrated by the long time required for neutralization.10

Effects of pH Increase in Mature Skin

One multicenter study measuring the natural pH on the surface of healthy skin found the arithmetic mean of pH values to be 4.9 with a 95% confidence interval between 4.1 and 5.8.9 The ideal acidity for the SC is an approximate pH of 5.4,1 which supports the presence of normal skin flora. However, it is well-known that an increase in pH is detected in skin as it matures, starting at anywhere from 50–80 years of age.11 Most likely, this decreased acidity is due to less efficient mechanisms for skin acidification; specifically, decreased NA+/H+ antiporter (NHE1) expression. NHE1 is one of three highly studied mechanisms for maintaining skin acidity and is assumed to be the predominant influence;12 the other two mechanisms include the breakdown of phospholipids into free fatty acids via phospholipase 2, and the breakdown of filaggrin into natural moisturizing factors such as urocanic acid. The resulting elevation of pH in mature skin alters multiple functions. Those included here are impairment of permeability barrier homeostasis, decreased skin integrity/cohesion, and increased susceptibility for microbial infection. Further, it has been found that the reduced buffering capacity of mature skin contributes to the increased sensitivity of skin to contact irritants and cleansing procedures.8

Impaired of permeability barrier homeostasis: An acidic pH is critical for normal epidermal barrier function and is in part due to two key lipid-processing enzymes, B-glucocerebrosidase and acid sphingomyelinase, which generate a family of ceramides from glucosylceramide and sphingomyelin precursors and exhibit low pH optima.13 An increase in skin pH results in defective lipid processing and the delayed maturation of lamellar membranes12 that form multilamellar sheets amidst the intracellular spaces of the SC. These sheets are critical to the mechanical and cohesive properties of the SC, enabling it to function as an effective water barrier.12 Further, this delayed barrier function allows for the easier penetration of topically applied products and delays barrier recovery after injury or insult to the skin.12, 13

Decreased skin integrity and cohesion: An acidic pH also promotes SC integrity and cohesion. As has been shown, compared with an acidic environment, a neutral pH environment enhances the tendency for the SC to be removed by tape stripping, i.e., integrity, as well as increases the amount of protein removed per stripping, i.e., cohesion.12 This impaired SC integrity/cohesion is due to the pH-dependent activation of serine proteases, which exhibit neutral pH optima.5, 13 Serine proteases become activated in the increased pH of mature skin and lead to the premature degradation of corneodesmosomes and hence, increased desquamation. 12, 14

Increased susceptibility for skin infections: Finally, the acidic pH of the SC restricts colonization by pathogenic flora and encourages the persistence of normal microbial flora. Pertinently, mature skin, intertriginous areas and chronically inflamed skin display an increased pH2 and hence, reduced resistance to pathogens.11

In summary, elderly skin commonly exhibits abnormalities in SC integrity/cohesion, permeability barrier homeostasis, and immune function due to the pH-influenced increase in serine protease-mediated degradation of corneodesmosomes, defects in lipid processing, and decrease in antibacterial activity, respectively.

SC Components and Buffering

Lipid content and sebum production: Early experimentation hypothesized that sebum contributes to the buffering capacity of skin in two ways: first, it protects the epidermis against the influence of alkali by slowing the exposure and penetration of acids or alkalis applied to the skin;15, 16 second, the fatty acids in sebum may act as a buffering system.17 Lincke et al.18 refuted this second hypothesis by demonstrating that the sebum had no relevant acid and a negligible alkali buffering capacity of around pH 9. Further challenging the hypothesis, a quicker neutralization was observed on delipidized skin than on untreated skin.15, 17

The brick-and-mortar model often is used to describe the SC’s protein-rich corneocytes embedded in a matrix of ceramides, cholesterol and fatty acids, and smaller amounts of cholesterol sulfates, glucosylceramides and phospholipids. As stated earlier, these lipids form multilamellar sheets amidst the intracellular spaces of the SC that are critical to its mechanical and cohesive properties, enabling it to function as an effective water barrier.12 Many authors agree that the overall lipid content of human skin decreases with age,19 although the proportion of different lipid classes seems to remain fairly constant.7

Sebaceous gland functioning has been found to decrease in association with concomitant decrease in endogenous androgen production.20 This is the likely the cause of decreased surface lipid levels in mature skin. In men, sebum levels remain essentially unchanged until the age of 80 years. In women, however, there is a gradual decrease in sebaceous secretion from menopause through the seventh decade, after which no appreciable change occurs.21 Assuming that the presence of sebum does slow the penetration of topical insults, and considering that mature skin has been shown to contain a decreased amount of lipids, it can be deduced that any topical insult would more easily overwhelm the buffering system of elderly skin.

Water: Vermeer et al.22 first demonstrated the importance of water-soluble constituents in the skin’s buffering ability. Water-soaked skin in which the water-soluble constituents were extracted demonstrated a significantly reduced neutralization capacity, indicating that water-soluble constituent(s) of the skin are major contributors to the buffering capacity.22 In younger skin, most water is bound to proteins and is appropriately termed bound water.23 Bound water is important for the structure and mechanical properties of many proteins and their mutual interactions. Water molecules that are not bound to proteins bind to each other and form tetrahedron or bulk water.23

In mature skin, water is mostly found in the tetrahedron form,24 and this lack of interaction between water and the surrounding molecules in mature skin leads to variations in the water-soluble portion of the SC, likely contributing to the decreased buffering capacity found in mature skin. In addition, this chemical change in the water explains why it is that mature SC has higher total water content than younger skin, yet is often dry and weathered.7

Proteins: Free amino acids (AA) in the water-soluble portion of the epidermis also have been shown to play a significant role in the neutralization of alkalis—and quickly, i.e., within the first 5 min of experimentation.25 The water-soluble, free AA on the skin surface may originate from five possible sources: eccrine sweat, the degradation of skin proteins, hair follicles, keratin hydrosylates and keratohyalin granule histidine-rich protein.

Sweat contains 0.05% AA, which remain on the surface of the skin after evaporation, although the specific AA found in sweat was not investigated. In addition, the degradation of skin proteins including proteins constituting the desmosomes could be a source for AA, such as serine, glycine and alanine. In hair follicles, citrulline, which is released by specific proteases, is recognized as a constituent of protein synthesized in the inner root sheath and medulla cells of the hair follicle. Citrulline is also found in proteins in the membrane of the corneocytes.26

Keratin hydrosylates may also produce free amino acids, although as the AA composition of keratin does not correspond with the composition of free AA found the SC.25, 26 Finally, the pool of free amino acids, urocanic acid and pyrrolidone carboxylic acid in mammalian SC has been shown to be derived principally or totally from the histidine-rich protein of the keratohyalin granules. The time course of appearance of free amino acids and breakdown of the histidine-rich protein are similar, as are the analyses of the free amino acids and the histidine-rich protein. Quantitative studies show that between 70% and 100% of the total SC free amino acids are derived from the histidine-rich protein.27

The majority of proteins in young skin are in helical conformation. This is in contrast to mature skin, which can show markedly altered protein conformation such as increased protein folding, resulting in less exposure to aliphatic residues to water.23, 24 Increased protein folding and the decreased interaction of proteins with water affects the concentration of AA in the SC, which as noted previously, likely plays an important role in the buffering capacity of skin.

In addition, the AA composition of proteins and free amino acids in mature skin differ significantly from that of young skin, and there is an increase in the overall hydrophobicity of amino acids in mature skin.28 As free amino acids are believed to play a key role in SC buffering capacity, this shift in composition, combined with evidence of altered protein tertiary protein structure provides insight into the diminished buffering capacity in mature skin.

It should also be noted that the increase in pH of aged skin will also change the fraction of AA in the SC that are associated or disassociated. Free AA work best as buffers at a pH that is equal to their pKa, i.e, the pH at which 50% of the AA associated and disassociated. Due to the increased baseline pH found in mature skin, the percentage of associated to disassociated AA changes, hence changing the effectiveness of the buffer.

Eccrine sweat glands: Eccrine sweat also initially accelerates the neutralization of alkalis.10, 22 Spier and Pasher25 suggest that the main buffering agents of sweat are lactic acid and amino acids. The lactic acid-lactate system in sweat has a highly efficient buffering capacity between pH 4 to 5.16 However, it has not been completely demonstrated that lactic acid is the main buffering agent in sweat or at the surface of the skin. Conversely, the contribution of AA to the buffering capacity of sweat and of the horny layer surface has thoroughly been investigated.22

With aging, the number of active eccrine sweat glands is reduced and the amount of sweat output per gland is diminished both by rate and amount. Morphologically, the secretory cells flatten and become atrophic, and a progressive accumulation of lipofuscin is found in the cytoplasm of the glandular epithelium.20 Therefore, any contribution of eccrine sweat to the buffering capacity would be decreased in aged skin due to the decreased output of sweat overall.


Skin’s exquisite buffering capacity has been widely studied in vitro and in vivo, yet further research must be conducted to better understand the exact mechanisms responsible. Experimentation reviewed here suggests that AAs are primarily responsible for the neutralization capacity of skin, although the exact sources for, as well as the types of, AA responsible for this capacity remain speculative. In addition, it seems that a sweat component increases the neutralization capacity of the epidermis; whether the buffering component of sweat is an additional AA or lactic acid remains unknown. And while additional components of the epidermis such as sebum do not seem to significantly participate as buffering agents in the epidermis, they may still play a role in the protection of skin from the harm of acids and bases.

After a thorough review of the studies investigating the buffering capacity of skin and the endogenous mechanisms for restoring and maintaining skin pH, it is interesting to note that the two topics have generally been investigated separately without looking for a commonality. In these authors’ views, it would not be surprising if the mechanisms responsible for maintaining skin pH influence the processes responsible for maintaining skin buffering capacity. The above rationale may shed light on the clinical correlation of increased pH and decreased buffering capacity seen in certain skin diseases29 and in mature skin.7

This theory is supported by the discovery that 70% to 100% of AAs of the SC are derived from the degradation of histidine-rich protein in keratohyalin granules, which is also one of the essential pathways involved in maintaining skin pH.3 This theory is further supported by the fact that decreasing pH levels in mature skin via acidic topical products has led to an increased buffering capacity and reduced skin sensitivity. One study in particular used a preparation acidified with citric acid/ammonium citrate buffer and demonstrated a significant shortening of the alkaline neutralization time in aged skin from 5.3 + 0.6 min to 4.9 + 0.5 min after four weeks of application.30 While more research must be conducted to determine the benefit of topical acidic therapy for mature skin, this application seems reasonable as many authors have demonstrated the use of acidic topic products or washes on patients with increased pH levels to help restore integrity/cohesion and barrier recovery.14

Taken together, the authors interpret this rich experimental literature, some dating years back, as leading the way to utilization of contemporary methods to further refine the industry’s insight into skin’s buffering capacity and aging skin. This capacity, when fully understood, may lead to not only the potential for decreasing the threat of exogenous acids and bases to aged skin, but also to the establishment of an experimental basis for optimizing the pH of many cosmetic, pharmacologic, metabolic and toxicologic situations and treatments for mature skin. Reproduction of the article without expressed consent is strictly prohibited.

1. E Heuss, Die reaktion des scheisses beim gesunden menschen, Monatsh. Prakt, Dermatol 14 343 (1892)
2. H Schade and A Marchionini, Zur physikalischen cheme der hautoberflache, Arch Dermatol Syphil 154 690 (1928)
3. M Kim, R Patel and A Shinn, Evaluation of gender difference in skin type and pH, J Dermatol Sci 41 153–156 (2006)
4. B Greener, A Hughes, N Bannister and J Douglas, Proteases and pH in chronic wounds, J Wound Care 14 2 59–61 (Feb 2005)
5. J Hachem, D Crumrine, J Fluhr, B Brown, K Feingold and P Elias, pH directly regulates epidermal permeability barrier homeostasis and stratum corneum integrity/cohesion, J Invest Dermatol 121 345–353 (2003)
6. P Agache, Measurement of skin surface acidity, P Agache, P Humbert and HI Maibach, eds., in Measuring Skin, Springer: Paris 84–86 (2004)
7. JM Waller and HI Maibach, Age and skin structure and function, a quantitative approach (II): Protein, glycosaminoglycan, water and lipid content and structure, Skin Res Technol 12 3 145–154 (Aug 2006)
8. W Raab, Skin cleansing in health and disease, Wien Med Wschr 141 suppl, 108: 4–10 (1990)
9. D Segger et al, Multicenter study on measurement of the natural pH of the skin surface, IFSCC Magazine 10 2 107–110 (2007)
10. W Burckhardt, Beitrage zur Ekzemfrage, II. Die rolle des alkali in pathogenese des ekzems speziell des gewerbeekzems, Arch F Dermat U Syph 173 155–167 (1935)
11. J Fore-Pfliger, The epidermal skin barrier: Implications for the wound care practitioner, part I, Advances in skin and wound care 17 8 417–425 (2004)
12. EH Choi et al, Stratum corneum acidification is impaired in moderately aged human and murine skin, J Invest Dermatol 127 12 2847–2856 (2007)
13. JP Hachem, D Crumrine, J Fluhr, BE Brown, KR Feingold and P Elias, pH directly regulates epidermal permeability barrier homeostasis and stratum corneum integrity/cohesion, J Invest Dermatol 121 345–353 (2003)
14. JL Leveque, P Corcuff, J de Rigal and P Agache, In vivo studies of the evolution of physical properties of the human skin with age, Int J Dermatol 23 5 322–329 (Jun 1984)
15. M Dunner, Der einfluss des hauttalges auf die alkaliabwehr der haut, Dermatologica 101 17–28 (1950) 16. E Fishberg and W Bierman, Acid base balance in sweat, J Biol Chem 97 433–441 (1932)
17. B McKenna, The composition of the surface skin fat (sebum) from the human forearm, J Invest Derm 15 33–37 (1950)
18. H Lincke, Beitrage zur chemie und biologie des hautoberflachenfetts, Arch f Dermat U Syph 188 453–481 (1949)
19. J Rogers, C Harding, A Mayo, J Banks and A Rawlings, Stratum corneum lipids: The effects of aging and the seasons, Arch Dermatol Res 288 765–770 (1996)
20. SV Pollack, The aging skin, J Fla Med Assoc 72 4 245–248 (1985) 21. PE Pochi, JS Strauss and DT Downing, Age-related changes in sebaceous gland activity, J Invest Dermatol 73 108–111 (1979)
22. D Vermeer, J Jong and J Lenestra, The significance of amino acids for the neutralization by the skin, Dermatologica 103 1–18 (1951)
23. M Gniadecka, OF Nielsen, DH Christensen and HC Wulf, Structure of water, proteins and lipids in intact human skin hair nail, J Invest Dermatol 110 393–398 (1998)
24. M Gniadecka, OF Nielsen, S Wessel, M Heidenheim, DH Christensen and HC Wulf, Water and protein structure in photo-aged and chronically skin, J Invest Dermatol 11 1129–1133 (1998)
25. H Spier and G Pascher, Quantitative untersuchungen uber die freien aminosauren der hautoberflache—Zur frage Ihrer genese, Klinische Wochenchrift 997–1000 (1953)
26. LL Peterson and KD Wuepper, Epidermal and hair follicle transglutaminases and crosslinking in skin. Mol Cell Biochem 58 1–2 99–111 (1984)
27. I Horii et al, Histidine-rich protein as a possible origin of free amino acids of stratum corneum, Curr Probl Dermatol 11 301–315 (1983)
28. T Jacobson, Y Yuksel, JC Geesin, JS Gordon, AT Lane and RW Gracy, Effects of aging and xerosis on the amino acid composition of human skin, J Invest Dermatol 95 296–300 (1990)
29. H Kurabayahi, K Tamura, I Machida and K Kubota, Inhibiting bacteria and skin pH in hemiplegia: Effects of washing hands with acidic mineral water, Am J Phys Med Rehabil 81 40–46 (2002)
30. W Meigel and M Sepehrmanesh, Untersuchung der pflegenden wirkung und der vertraglichkeit einer crème/loti bei alteren patienten mit trockenem hautzustand, Dtsch Derm 42 1235–1241 (1994)

* The present article has been adapted from J Levin and HI Maibach, Human buffering capacity considerations in the elderly, in: Textbook of Aging Skin, 1st edn, M Farage, K Miller and H Maibach, eds, Springer-verlag: Berlin/Heidelberg (2010) pp 139–145.

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Biography: Howard I. Maibach, MD, University of California, San Francisco

Howard I. Maibach, MD, is a professor of derma­tology at the University of California School of Medicine, San Francisco. His labor­atory has been interested in and has published exten­sively on derm­ato­pharma­cology and dermatotoxicology.

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