A Dermatological View—Percutaneous Penetration of Amino Acids

Skin care products containing amino acids often promote the benefits conferred on the skin by these molecules. Natural amino acids found in the skin have been found to improve the health of skin through antioxidation, membrane stabilization and increasing skin’s natural moisturizing factor (NMF),1 a compound known to increase hydration and firmness of skin. In addition, amino acids in the stratum corneum have been found to increase the penetration of water to lipids, which plumps skin and decreases the appearance of wrinkles.1 However, limited information is available on percutaneous absorption of amino acids, which this column will quantify by assembling previously published data.

Researchers performed a literature search using PubMed and EMBASE at the library at University of California, San Francisco, to find studies focused on amino acid absorption. Emphasis was placed on studies that included quantitative data on amino acid concentration, either within skin layers or in the acceptor solution of a diffusion chamber (DC). Data found on this topic was largely from in vitro experiments with animal skin, as measuring concentration in an acceptor solution is simpler and more definitive than measuring the quantity in human blood or a biopsy sample. Moreover, the methods of quantification varied, making comparison difficult. Permeability coefficients calculated from in vitro studies at a neutral pH ranged from 0.162 to 10 x 10-5 cm/hr and percent absorption calculated from in vivo studies ranged from 27–96%. This suggests that the amino acids contained in creams and lotions may be readily absorbed; however, the precise amount (and benefit) has yet to be characterized. The following studies are organized by test method and substrate.

Rodent Skin In vitro

Much of the data involving skin penetration was conducted in vitro using a Franz diffusion chamber (FD-C) with rodent skin suspended above an acceptor solution and the amino acid applied to the skin. In this experiment, concentrations of amino acids in the acceptor solution quantify their absorption. The experiment measures the amount of amino acid that crosses a non-human skin sample; it does not measure the amount retained. Therefore, this design limits applicability to human skin in vivo.2, 3

Hatanaka et al. conducted in vitro testing of the amino acids L-alanine, valine, isoleucine, leucine, lysine and spartic acid using FD-C and rat skin.2 The permeability coefficients (10 x 10-5 cm/hr) were: alanine, 0.507; valine, 2.034 (9–25% μg/cm2); isoleucine, 0.162; leucine, 0.163; lysine, 0.1554; and aspartic acid, 0.4206. These values were calculated from the measured potential difference and used as a marker for amino acid concentration. The researchers concluded that absorption depended on neutrality, molecular weight and pH of the solution; permeability coefficients differed with predominance of different zwitterions.

Ruland and Kreuter also conducted in vitro testing using FD-C, but with mouse skin. They found differing permeability coefficients that did not depend on neutrality or molecular weight as found by Hatanaka et al., but still differed with pH of the solution. They found the following permeability coefficients (10 x 10-5 cm/hr at pH 7.4): glycine, 3.9; alanine, 5.5; valine, 1.3; leucine, 2.9; isoleucine, 1.3; serine, 3.0; threonine, 1.3; aspartic acid, 0.8; asparagine, 3.5; glutamine, 5.0; glutamic acid, 1.0; lysine, 2.1; arginine, 10.0; histidine, 2.0; tryptophan, 1.5; phenylalanine, 3.0; tyrosine, 1.6; proline, 2.7; methionine, 3.1; and cystine, 1.9.3 Alkaline solutions increase permeability. This study used infinite doses, which is impractical for use in human application.

Human In vivo

Coderch et al. looked at human in vivo data using sequential tape stripping on volunteers to determine the amount absorbed. As amino acids are always present in skin, the investigators sought to quantify their increase after application, requiring enough absorption to reach the limit of quantification (LOQ).1 An amino acid autoanalyzer and high performance liquid chromatography, which measures amino acid content of the extracted solutions, were used. The researchers quantified the amino acids aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine and arginine. They found that threonine absorbed at 85.4%, isoleucine at 96.1% and lysine at 86.5%. Only the percent absorbance was calculated for these amino acids because they were present in undetectable concentrations prior to the application of amino acids, making detection of their presence postapplication an indication of successful penetration.

The study showed that chemical structure played little role in absorption, with the exception of isoleucine, which did not penetrate as well into the deeper skin layers. In some of the other experiments discussed, penetration was found to be dependent upon the charge (or neutrality) and molecular weight, and small amounts of amino acids were absorbed, as determined by increased concentrations over the baseline; however, increased levels in the skin were not retained for prolonged periods, i.e., there was no reservoir effect.

Human Skin In vitro

A recent experiment looked at the absorption of the amino acid taurine. An FD-C was used, and the researchers saw a 27% absorption of taurine at 1% in a propylene glycol cream. The taurine diffused quickly, and the relative concentrations of the amino acid between skin layers remained constant before and after exogenous application, presumably due to differential distribution of the taurine transporter (TAUT).4 Absorption was presumed to be by these hydrophilic pores and solvent drag. The taurine content was measured directly by capillary electrophoresis.


Experiments provide conflicting data, some showing that amino acid absorption depends upon neutrality, molecular weight and pH of the solution,2 while Coderch et al. found that the chemical structure plays a small role in absorption;1 Ruland and Kreuter found that amino acid permeability does not depend on hydrophobicity.3 Permeability coefficients calculated from in vitro studies at neutral pH ranged from 0.162 to 10 x 105 cm/hr,2, 3 and percent absorption calculated from in vivo studies ranged from 27–96%.1, 4 The results did not vary significantly among different amino acids in the same experimental design, but there was a significant difference in the results provided by different investigators.

These studies lack much information about the absorption of amino acids. There seems to be a consensus that the amino acids travel through hydrophilic pores and that at least some have specific transporters that lead to differences in concentration. However, factors leading to increased penetration and therapeutic benefit remain inconclusive.

It is notable that these studies did not use a consistent measure of amino acid concentrations. Hatanaka et al. measured potential difference as a marker of amino acid concentration, and Coderch et al. used sequential tape stripping on human volunteers to determine cutaneous concentrations. Ruland and Kreuter used an infinite dose model, which is not relevant for topical application from finite exposure; therefore, the clinical applicability is limited by the compounds themselves.

Taken together, amino acids penetrate skin. The next step is to quantify kinetics, which can be best accomplished using radiolabeling to detect where the amino acids are within the skin layers. Researchers also should relate amino acid to skin physiology and pharmacology. Radiolabels on stable isotopes—with liquid scintillation counting and, if necessary for detection, attenuated mass spectroscopy—should provide definitive data and stabilize the divergent literature estimates.

Once the penetration of amino acids is understood, researchers can determine whether their addition to skin care products will adequately increase the concentration in the consumer’s skin to provide the benefits that have been conveyed to them.


Send e-mail to CT_author@allured.com.

  1. L Coderch, M Oliva, L Pons and JL Parra, Percutaneous Penetration in Vivo of Amino Acids, Int J of Pharmaceutics 111(1) 7–14 (1994)
  2. T Hatanaka et al, Influence of pH on Skin Permeation of Amino Acids, J Pharmacy and Pharmacology 48(7) 675–679 (1996)
  3. A Ruland and J Kreuter, Transdermal Permeability and Skin Accumulation of Amino Acids, Int J Pharmaceutics 72(2) 149–155 (1991)
  4. DL Da Silva et al, Penetration Profile of Taurine in the Human Skin and its Distribution in Skin Layers, Pharmaceutical Research 25(8) 1846–1850 (2008)
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