Abstract
Skin barrier function impairment and inflammation promote allergen invasion through the skin, leading to sensitization and exacerbation of allergic diseases. Intake of linseed oil, an oil rich in alpha-linolenic acid (ALA), suppresses inflammation and allergic symptoms. To our knowledge, the effects of diacylglycerol-enriched ALA (ALA-DAG) oil intake on skin properties and allergic symptoms have not been evaluated. We performed a double-blind, randomized, placebo-controlled, parallel-group study of 60 individuals aged 20–59 years with mild skin discomfort, including dryness, itching, and redness, to investigate the effects of ALA-DAG intake on skin and allergic symptoms. Participants were divided into two groups treated with either 2.5 g/day of ALA-DAG or placebo oil for 8 weeks. The skin properties were measured at baseline and at 8 weeks. Allergic symptoms were measured at 4 and 8 weeks. Compared with placebo oil intake, ALA-DAG intake increased skin hydration in the cheek, reduced nasal congestion and nose itchiness, and decreased mite-specific immunoglobulin E in the blood. Subgroup analysis showed that participants who were positive for mite allergen sensitization had reduced facial redness after ingesting ALA-DAG. These findings suggest that ALA-DAG intake improves skin properties and alleviates allergic symptoms.
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Data availability
The dataset from which the current study is not available to public for confidentiality reason, since the participants in this study agreed to use the data only for the analysis of present study when the study was informed and would not be shared with third parties, but is available from the corresponding author upon reasonable request.
References
Campbell, D. E. & Mehr, S. Fifty years of allergy: 1965–2015. J. Paediatr. Child Health 51, 91–93. https://doi.org/10.1111/jpc.12806 (2015).
Platts-Mills, T. A. The allergy epidemics: 1870–2010. J. Allergy Clin. Immunol. 136, 3–13. https://doi.org/10.1016/j.jaci.2015.03.048 (2015).
Gutowska-Slesik, J., Samolinski, B. & Krzych-Falta, E. The increase in allergic conditions based on a review of literature. Postepy Dermatol. Alergol. 40, 1–7. https://doi.org/10.5114/ada.2022.119009 (2023).
Pappas, A., Liakou, A. & Zouboulis, C. C. Nutrition and skin. Rev. Endocr. Metab. Disord. 17, 443–448. https://doi.org/10.1007/s11154-016-9374-z (2016).
Maarouf, M., Maarouf, C. L., Yosipovitch, G. & Shi, V. Y. The impact of stress on epidermal barrier function: an evidence-based review. Br. J. Dermatol. 181, 1129–1137. https://doi.org/10.1111/bjd.17605 (2019).
Celebi Sozener, Z., Cevhertas, L., Nadeau, K., Akdis, M. & Akdis, C. A. Environmental factors in epithelial barrier dysfunction. J. Allergy Clin. Immunol. 145, 1517–1528. https://doi.org/10.1016/j.jaci.2020.04.024 (2020).
Matsumoto, K. & Saito, H. Epicutaneous immunity and onset of allergic diseases – per-“eczema”tous sensitization drives the allergy march. Allergol. Int. 62, 291–296. https://doi.org/10.2332/allergolint.13-RAI-0603 (2013).
Czarnowicki, T., Krueger, J. G. & Guttman-Yassky, E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J. Allergy Clin. Immunol. 139, 1723–1734. https://doi.org/10.1016/j.jaci.2017.04.004 (2017).
Davidson, W. F. et al. Report from the national institute of allergy and infectious diseases workshop on “Atopic dermatitis and the atopic march: Mechanisms and interventions”. J. Allergy Clin. Immunol. 143, 894–913. https://doi.org/10.1016/j.jaci.2019.01.003 (2019).
Saeki, H. et al. Clinical practice guidelines for the management of atopic dermatitis 2016. J. Dermatol. 43, 1117–1145. https://doi.org/10.1111/1346-8138.13392 (2016).
Minami, T. et al. Regional differences in the prevalence of sensitization to environmental allergens: Analysis on IgE antibody testing conducted at major clinical testing laboratories throughout Japan from 2002 to 2011. Allergol. Int. 68, 440–449. https://doi.org/10.1016/j.alit.2019.03.008 (2019).
Kelley, D. S. Modulation of human immune and inflammatory responses by dietary fatty acids. Nutrition 17, 669–673. https://doi.org/10.1016/s0899-9007(01)00576-7 (2001).
Arita, M. Mediator lipidomics in acute inflammation and resolution. J. Biochem. 152, 313–319. https://doi.org/10.1093/jb/mvs092 (2012).
Roper, R. L., Brown, D. M. & Phipps, R. P. Prostaglandin E2 promotes B lymphocyte Ig isotype switching to IgE. J. Immunol. 154, 162–170 (1995).
Buckley, C. D., Gilroy, D. W. & Serhan, C. N. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40, 315–327. https://doi.org/10.1016/j.immuni.2014.02.009 (2014).
Kunisawa, J. et al. Dietary omega3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut. Sci. Rep. 5, 9750. https://doi.org/10.1038/srep09750 (2015).
Nagatake, T. et al. The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. J. Allergy Clin. Immunol. https://doi.org/10.1016/j.jaci.2017.09.053 (2018).
Hirakata, T. et al. Dietary omega-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating T(h)2 immune responses. FASEB J. 33, 3392–3403. https://doi.org/10.1096/fj.201801805R (2019).
Sawane, K. et al. Dietary omega-3 fatty acid dampens allergic rhinitis via eosinophilic production of the anti-allergic lipid mediator 15-hydroxyeicosapentaenoic acid in mice. Nutrients https://doi.org/10.3390/nu11122868 (2019).
De Spirt, S. et al. Intervention with flaxseed and borage oil supplements modulates skin condition in women. Br. J. Nutr. 101, 440–445. https://doi.org/10.1017/S0007114508020321 (2009).
Neukam, K. et al. Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition. Skin Pharmacol. Physiol. 24, 67–74. https://doi.org/10.1159/000321442 (2011).
D’alonzo, R., Kozarek, W. & Wade, R. Glyceride composition of processed fats and oils as determined by glass capillary gas chromatography. J. Am. Oil Chem. Soc. 59, 292–295 (1982).
Flickinger, B. D. & Matsuo, N. Nutritional characteristics of DAG oil. Lipids 38, 129–132. https://doi.org/10.1007/s11745-003-1042-8 (2003).
Yamanaka, N. et al. Alpha-linolenic acid-enriched diacylglycerol oil suppresses the postprandial serum triglyceride level-a randomized, double-blind, placebo-controlled, crossover study. J. Nutr. Sci. Vitaminol. (Tokyo) 62, 402–408. https://doi.org/10.3177/jnsv.62.402 (2016).
Saito, S., Mori, A., Osaki, N. & Katsuragi, Y. Diacylglycerol enhances the effects of alpha-linolenic acid against visceral fat: a double-blind randomized controlled trial. Obesity (Silver Spring) 25, 1667–1675. https://doi.org/10.1002/oby.21938 (2017).
Schmitz, G. & Ecker, J. The opposing effects of n-3 and n-6 fatty acids. Prog. Lipid Res. 47, 147–155. https://doi.org/10.1016/j.plipres.2007.12.004 (2008).
van den Elsen, L., Garssen, J. & Willemsen, L. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease. Curr. Pharm. Des. 18, 2375–2392. https://doi.org/10.2174/138161212800165960 (2012).
Fussbroich, D. et al. A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma. Lipids Health Dis. 18, 16. https://doi.org/10.1186/s12944-018-0947-6 (2019).
Akutsu, N. et al. Functional characteristics of the skin surface of children approaching puberty: age and seasonal influences. Acta Derm. Venereol. 89, 21–27. https://doi.org/10.2340/00015555-0548 (2009).
Ishikawa, J. et al. Variations in the ceramide profile in different seasons and regions of the body contribute to stratum corneum functions. Arch. Dermatol. Res. 305, 151–162. https://doi.org/10.1007/s00403-012-1286-5 (2013).
Jakasa, I., de Jongh, C. M., Verberk, M. M., Bos, J. D. & Kezic, S. Percutaneous penetration of sodium lauryl sulphate is increased in uninvolved skin of patients with atopic dermatitis compared with control subjects. Br. J. Dermatol. 155, 104–109. https://doi.org/10.1111/j.1365-2133.2006.07319.x (2006).
Darlenski, R., Kazandjieva, J., Tsankov, N. & Fluhr, J. W. Acute irritant threshold correlates with barrier function, skin hydration and contact hypersensitivity in atopic dermatitis and rosacea. Exp. Dermatol. 22, 752–753. https://doi.org/10.1111/exd.12251 (2013).
Montero-Vilchez, T. et al. Skin barrier function in psoriasis and atopic dermatitis: transepidermal water loss and temperature as useful tools to assess disease severity. J. Clin. Med. https://doi.org/10.3390/jcm10020359 (2021).
Kulthanan, K., Chularojanamontri, L., Manapajon, A. & Nuchkull, P. Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites. Asian Pac. J. Allergy Immunol. 29, 318–326 (2011).
Dey, D. et al. Sensitization to common aeroallergens in the atopic population of West Bengal, India: an investigation by skin prick test. Int. Arch. Allergy Immunol. 178, 60–65. https://doi.org/10.1159/000492584 (2019).
Ha, E. K. et al. Atopic dermatitis: Correlation of severity with allergic sensitization and eosinophilia. Allergy Asthma Proc. 41, 428–435. https://doi.org/10.2500/aap.2020.41.200067 (2020).
Tanaka, J. et al. Prevalence of inhaled allergen-specific IgE antibody positivity in the healthy Japanese population. Allergol. Int. 71, 117–124. https://doi.org/10.1016/j.alit.2021.08.009 (2022).
Deckers, J. et al. Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells. J. Allergy Clin. Immunol. 140, 1364–1377. https://doi.org/10.1016/j.jaci.2016.12.970 (2017).
Uehara, Y., Inoue, T., Ota, N., Ikeda, S. & Murase, T. Non-invasive evaluation of subjective sensitive skin by transcriptomics using mRNA in skin surface lipids. Exp. Dermatol. 31, 172–181. https://doi.org/10.1111/exd.14459 (2022).
Inoue, T. et al. Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids. Commun. Biol. 5, 215. https://doi.org/10.1038/s42003-022-03154-w (2022).
Yamamoto-Hanada, K. et al. mRNAs in skin surface lipids unveiled atopic dermatitis at 1 month. J. Eur. Acad. Dermatol. Venereol. 37, 1385–1395. https://doi.org/10.1111/jdv.19017 (2023).
Sheldrick, E. L. et al. Peroxisome-proliferator-activated receptors and the control of levels of prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus. Biochem. J. 406, 175–183. https://doi.org/10.1042/BJ20070089 (2007).
Thorn, C. F., Grosser, T., Klein, T. E. & Altman, R. B. PharmGKB summary: very important pharmacogene information for PTGS2. Pharmacogenet. Genomics 21, 607–613. https://doi.org/10.1097/FPC.0b013e3283415515 (2011).
Gijon, M. A., Riekhof, W. R., Zarini, S., Murphy, R. C. & Voelker, D. R. Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils. J. Biol. Chem. 283, 30235–30245. https://doi.org/10.1074/jbc.M806194200 (2008).
Matsuda, S. et al. Member of the membrane-bound O-acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity. Genes Cells 13, 879–888. https://doi.org/10.1111/j.1365-2443.2008.01212.x (2008).
Kikuchi, M., Igarashi, T., Sato, H. & Fujimura, T. AIC Jeju. 88. (2017)
Higaki, Y. et al. The Japanese version of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J. Dermatol. 29, 693–698. https://doi.org/10.1111/j.1346-8138.2002.tb00205.x (2002).
Chren, M. M., Lasek, R. J., Sahay, A. P. & Sands, L. P. Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J. Cutan. Med. Surg. 5, 105–110. https://doi.org/10.1007/BF02737863 (2001).
Okuda, M. et al. Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires. Acta Otolaryngol. 125, 736–744. https://doi.org/10.1080/00016480510026944 (2005).
Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).
Shima, K. et al. Non-invasive transcriptomic analysis using mRNAs in skin surface lipids obtained from children with mild-to-moderate atopic dermatitis. J. Eur. Acad. Dermatol. Venereol. 36, 1477–1485. https://doi.org/10.1111/jdv.18173 (2022).
da Huang, W., Sherman, B. T. & Lempicki, R. A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1–13. https://doi.org/10.1093/nar/gkn923 (2009).
da Huang, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57. https://doi.org/10.1038/nprot.2008.211 (2009).
Acknowledgements
We thank Ms. Mamiko Kikuchi at Skin Care Research, Kao Corporation, for advice on skin color assessment techniques; Dr. Yasutoshi Ando at Human Health Care Products Research, Kao Corporation, for technical advice for blood lipid analysis; and Dr. Kazuya Kouzuma and Dr. Toru Yamaguchi at Human Health Care Products Research for appropriate advice on subject eligibility and statistical analysis. We also thank SciTechEdit International for English language editing.
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Conceptualization: SF, KeS, KaS, and JI; Data curation: SF, YoS, KeS, AS, HF, and YuS; Formal analysis: SF, YoS, KeS, AS, HF, and YuS; Investigation: SF, YoS, KeS, AS, KaS, HF, and YuS; Methodology: SF, YoS, KeS, AS, KaS, KM, and JI; Resources: AS, and KaS; Supervision: NO and TY; Visualization: SF, and MH; Writing—original draft: SF and HM; Writing—review & editing: KM, SS, JI, and TY.
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Fukagawa, S., Shimotoyodome, Y., Sayama, K. et al. Effects of diacylglycerol-enriched alpha-linolenic acid oil on skin properties in mild skin discomfort: a randomized, double-blind, placebo-controlled study. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34887-3
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DOI: https://doi.org/10.1038/s41598-025-34887-3


