Nutr Res Pract.  2016 Aug;10(4):398-403. 10.4162/nrp.2016.10.4.398.

Associations among plasma vitamin C, epidermal ceramide and clinical severity of atopic dermatitis

• Shin J
• Kim YJ
• Kwon O
• Kim NI
• Cho Y

• KMID: 2390142
• DOI: http://doi.org/10.4162/nrp.2016.10.4.398

Abstract

BACKGROUND/OBJECTIVES
Atopic dermatitis (AD), a chronic inflammatory skin disease, is accompanied by disruption of the epidermal lipid barrier, of which ceramide (Cer) is the major component. Recently it was reported that vitamin C is essential for de novo synthesis of Cer in the epidermis and that the level of vitamin C in plasma is decreased in AD. The objective of this study was to determine the associations among clinical severity, vitamin C in either plasma or epidermis, and Cer in the epidermis of patients with AD.
SUBJECTS/METHODS
A total of 17 patients (11 male and 6 female) aged 20-42 years were enrolled. The clinical severity of AD was assessed according to the SCORAD (SCORing Atopic Dermatitis) system. Levels of vitamin C were determined in plasma and biopsies of lesional epidermis. Levels of epidermal lipids, including Cer, were determined from tape-stripped lesional epidermis.
RESULTS
The clinical severity of patients ranged between 0.1 and 45 (mild to severe AD) based on the SCORAD system. As the SCORAD score increased, the level of vitamin C in the plasma, but not in the epidermis, decreased, and levels of total Cer and Cer2, the major Cer species in the epidermis, also decreased. There was also a positive association between level of vitamin C in the plasma and level of total Cer in the epidermis. However, levels of epidermal total lipids including triglyceride, cholesterol, and free fatty acid (FFA) were not associated with either SCORAD score or level of vitamin C in the plasma of all subjects.
CONCLUSIONS
As the clinical severity of AD increased, level of vitamin C in the plasma and level of epidermal Cer decreased, and there was a positive association between these two parameters, implying associations among plasma vitamin C, epidermal Cer, and the clinical severity of AD.

Keyword

Atopic dermatitis; vitamin C; ceramide; clinical severity

MeSH Terms

Ascorbic Acid*
Biopsy
Cholesterol
Dermatitis, Atopic*
Epidermis
Humans
Male
Plasma*
Skin Diseases
Triglycerides
Vitamins*
Ascorbic Acid
Cholesterol
Vitamins

Figure

• 

  Fig. 1 Association of plasma vitamin C with total ceramide in the epidermis of subjects with atopic dermatitis Vitamin C level in plasma was determined by high performance liquid chromatography-electrochemical detection (HPLC-ECD). Epidermal lipids of subjects with atopic dermatitis (AD) (n = 17) were collected by tape stripping and total ceramide (Cer) was fractionated by high-performance thin-layer chromatography (HPTLC). Association of plasma vitamin C with total Cer in the epidermis of subjects with AD was determined by Pearson's correlation analysis.

Reference

1. Addor FA, Takaoka R, Rivitti EA, Aoki V. Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity. Int J Dermatol. 2012; 51:672–676.

2. Darlenski R, Kazandjieva J, Hristakieva E, Fluhr JW. Atopic dermatitis as a systemic disease. Clin Dermatol. 2014; 32:409–413.

3. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol. 1983; 80:Suppl. 44s–49s.

4. Weerheim A, Ponec M. Determination of stratum corneum lipid profile by tape stripping in combination with high-performance thin-layer chromatography. Arch Dermatol Res. 2001; 293:191–199.

5. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998; 78:27–30.

6. Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol. 1991; 96:523–526.

7. Matsumoto M, Umemoto N, Sugiura H, Uehara M. Difference in ceramide composition between "dry" and "normal" skin in patients with atopic dermatitis. Acta Derm Venereol. 1999; 79:246–247.

8. Merrill AH Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem. 2002; 277:25843–25846.

9. Garner WL, Oyatsu Y, Zuccaro C, Rodriquez JL, Smith DJ, Marcelo CL. The effect of essential fatty acid supplementation on keratinocyte replication. Prostaglandins Leukot Essent Fatty Acids. 1995; 52:349–355.

10. Zineb R, Zhor B, Odile W, Marthe RR. Distinct, tissue-specific regulation of vitamin D receptor in the intestine, kidney, and skin by dietary calcium and vitamin D. Endocrinology. 1998; 139:1844–1852.

11. Hennings H, Michael D, Cheng C, Steinert P, Holbrook K, Yuspa SH. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980; 19:245–254.

12. Uchida Y, Behne M, Quiec D, Elias PM, Holleran WM. Vitamin C stimulates sphingolipid production and markers of barrier formation in submerged human keratinocyte cultures. J Invest Dermatol. 2001; 117:1307–1313.

13. Ponec M, Weerheim A, Kempenaar J, Mulder A, Gooris GS, Bouwstra J, Mommaas AM. The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C. J Invest Dermatol. 1997; 109:348–355.

14. Sivaranjani N, Rao SV, Rajeev G. Role of reactive oxygen species and antioxidants in atopic dermatitis. J Clin Diagn Res. 2013; 7:2683–2685.

15. Leveque N, Robin S, Muret P, Mac-Mary S, Makki S, Humbert P. High iron and low ascorbic acid concentrations in the dermis of atopic dermatitis patients. Dermatology. 2003; 207:261–264.

16. Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol. 2002; 119:166–173.

17. Shindo Y, Witt E, Han D, Epstein W, Packer L. Enzymic and nonenzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol. 1994; 102:122–124.

18. Kunz B, Oranje AP, Labrèze L, Stalder JF, Ring J, Taïeb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1997; 195:10–19.

19. Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B. Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J Am Acad Dermatol. 2003; 49:198–205.

20. Benzie I, Strain JJ. Effect of vitamin C supplementation on concentrations of vitamins C and E in fasting plasma. Asia Pac J Clin Nutr. 1999; 8:207–210.

21. Dhariwal KR, Hartzell WO, Levine M. Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. Am J Clin Nutr. 1991; 54:712–716.

22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193:265–275.

23. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226:497–509.

24. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S. Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res. 2000; 41:2071–2082.

25. Kim H, Lee J, Cho Y. Dietary sericin enhances epidermal levels of glucosylceramides and ceramides with up-regulating protein expressions of glucosylceramide synthase, beta-glucocerebrosidase and acidic sphingomyelinase in NC/Nga mice. Nutr Res. 2012; 32:956–964.

26. Chen H, Mendelsohn R, Rerek ME, Moore DJ. Fourier transform infrared spectroscopy and differential scanning calorimetry studies of fatty acid homogeneous ceramide 2. Biochim Biophys Acta. 2000; 1468:293–303.

27. Benzie IF. Vitamin C: prospective functional markers for defining optimal nutritional status. Proc Nutr Soc. 1999; 58:469–476.

28. Angelova-Fischer I, Mannheimer AC, Hinder A, Ruether A, Franke A, Neubert RH, Fischer TW, Zillikens D. Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling. Exp Dermatol. 2011; 20:351–356.

29. Hara J, Higuchi K, Okamoto R, Kawashima M, Imokawa G. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol. 2000; 115:406–413.

30. Tawada C, Kanoh H, Nakamura M, Mizutani Y, Fujisawa T, Banno Y, Seishima M. Interferon-γ decreases ceramides with long-chain fatty acids: possible involvement in atopic dermatitis and psoriasis. J Invest Dermatol. 2014; 134:712–718.

31. Pinnel SR, Murad S, Darr D. Induction of collagen synthesis by ascorbic acid. A possible mechanism. Arch Dermatol. 1987; 123:1684–1686.