{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:14:12Z","timestamp":1791281652538,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,5]],"date-time":"2023-08-05T00:00:00Z","timestamp":1691193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nissui Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Dihomo-\u03b3-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid that has been shown to have anti-inflammatory and anti-allergic effects in mice and cell study. To date, however, no human intervention study has examined the effects of DGLA. Therefore, we investigated the effects of DGLA on pollen-induced allergic symptoms in healthy adults. We performed a randomized, double-blind, placebo-controlled, parallel-group study comprising healthy Japanese men and women. Each subject received four 250 mg capsules providing 314 mg DGLA\/day (DGLA group, n = 18) or olive oil (placebo group, n = 15) for 15 weeks. The primary outcomes, classification of the severity of allergic rhinitis symptoms (CSARS), and the Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) served as symptom scores during the pollen season. In the DGLA group, the cedar pollen associated symptoms of sneezing and a blocked nose in the CSARS were significantly lower than those in the placebo group (p &lt; 0.05, p &lt; 0.01, respectively). Significant trends were observed the symptoms of runny nose in the CSARS and total symptom score (TSS) in the JRQLQ for cedar pollen (p &lt; 0.1). To our knowledge, this is the first study to report the effects of DGLA in humans, and the results suggest that DGLA is effective in reducing allergic symptoms caused by pollen.<\/jats:p>","DOI":"10.3390\/nu15153465","type":"journal-article","created":{"date-parts":[[2023,8,5]],"date-time":"2023-08-05T10:25:36Z","timestamp":1691231136000},"page":"3465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Supplementation of Dihomo-\u03b3-Linolenic Acid for Pollen-Induced Allergic Symptoms in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"15","author":[{"given":"Kaori","family":"Yokoi","sequence":"first","affiliation":[{"name":"Food Function R&D Center, Nissui Corporation, Tokyo 192-0919, Japan"},{"name":"Laboratory of Food Chemistry, Yokohama University of Pharmacy, Yokohama 245-0066, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yanagimoto","sequence":"additional","affiliation":[{"name":"Food Function R&D Center, Nissui Corporation, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohsuke","family":"Hayamizu","sequence":"additional","affiliation":[{"name":"Laboratory of Food Chemistry, Yokohama University of Pharmacy, Yokohama 245-0066, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1093\/protein\/gzp058","article-title":"Engineering of a novel hybrid enzyme: An anti-inflammatory drug target with triple catalytic activities directly converting arachidonic acid into the inflammatory prostaglandin E2","volume":"22","author":"Ruan","year":"2009","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2174\/138920106779116874","article-title":"Gamma linolenic acid: An antiinflammatory omega-6 fatty acid","volume":"7","author":"Kapoor","year":"2006","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.plefa.2018.03.004","article-title":"Omega-6 fatty acids and inflammation","volume":"132","author":"Innes","year":"2018","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3181\/0711-MR-311","article-title":"The importance of the omega-6\/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases","volume":"233","author":"Simopoulos","year":"2008","journal-title":"Exp. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1093\/carcin\/24.3.385","article-title":"The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE(2) synthesis and cytotoxicity in human colorectal carcinoma cell lines","volume":"24","author":"Dommels","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/CMR.0b013e328339d8ac","article-title":"Similar antineoplastic effects of nimesulide, a selective COX-2 inhibitor, and prostaglandin E1 on B16-F10 murine melanoma cells","volume":"20","author":"Tabolacci","year":"2010","journal-title":"Melanoma Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1042\/bj20011798","article-title":"Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: Implications for cellular synthesis of prostaglandin E1 and prostaglandin E2","volume":"365","author":"Levin","year":"2002","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/jn\/128.9.1411","article-title":"Importance of dietary gamma-linolenic acid in human health and nutrition","volume":"128","author":"Fan","year":"1998","journal-title":"J. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1631\/jzus.B1101007","article-title":"Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow","volume":"12","author":"Li","year":"2011","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1007\/s11095-011-0409-6","article-title":"PLGA microparticles encapsulating prostaglandin E1-hydroxypropyl-\u03b2-cyclodextrin (PGE1-HP\u03b2CD) complex for the treatment of pulmonary arterial hypertension (PAH)","volume":"28","author":"Gupta","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2011.01.002","article-title":"A high ratio of dietary n-6\/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer","volume":"31","author":"Williams","year":"2011","journal-title":"Nutr. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1046\/j.1365-2567.2003.01749.x","article-title":"Dihomo-gamma-linolenic acid inhibits tumour necrosis factor-alpha production by human leucocytes independently of cyclooxygenase activity","volume":"110","author":"Dooper","year":"2003","journal-title":"Immunology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8697","DOI":"10.1007\/s00253-014-5949-3","article-title":"Oral administration of whole dihomo-\u03b3-linolenic acid-producing Saccharomyces cerevisiae suppresses cutaneous inflammatory responses induced by croton oil application in mice","volume":"98","author":"Watanabe","year":"2014","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1476-511X-11-25","article-title":"Multiple roles of dihomo-\u03b3-linolenic acid against proliferation diseases","volume":"11","author":"Wang","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mustonen, A.M., and Nieminen, P. (2023). Dihomo-\u03b3-Linolenic Acid (20:3n-6)-Metabolism, Derivatives, and Potential Significance in Chronic Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032116"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ejphar.2016.04.020","article-title":"Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes","volume":"785","author":"Sergeant","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1464-5491.1990.tb01451.x","article-title":"Pathogenesis of diabetic neuropathy: The role of the n-6 essential fatty acids and their eicosanoid derivatives","volume":"7","author":"Jamal","year":"1990","journal-title":"Diabet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1002\/art.1780391106","article-title":"gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial","volume":"39","author":"Zurier","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/ajcn\/77.4.943","article-title":"Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis--a randomized controlled trial in infants at high familial risk","volume":"77","author":"Thijs","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1272\/jnms.JNMS.2021_88-317","article-title":"Nutrition and Atopic Dermatitis","volume":"88","author":"Kanda","year":"2021","journal-title":"J. Nippon. Med. Sch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"480","DOI":"10.5551\/jat.No430","article-title":"Anti-atherosclerotic effects of dihomo-gamma-linolenic acid in ApoE-deficient mice","volume":"16","author":"Takai","year":"2009","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12944-017-0542-2","article-title":"Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure","volume":"16","author":"Ouchi","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nilsen, D.W.T., Myhre, P.L., Kalstad, A., Schmidt, E.B., Arnesen, H., and Seljeflot, I. (2021). Serum Levels of Dihomo-Gamma (\u03b3)-Linolenic Acid (DGLA) Are Inversely Associated with Linoleic Acid and Total Death in Elderly Patients with a Recent Myocardial Infarction. Nutrients, 13.","DOI":"10.3390\/nu13103475"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s11746-000-0178-2","article-title":"Industrial production of dihomo-\u03b3-linolenic acid by a \u03945 desaturase-defective mutant of Mortierella alpina 1S-4 Fungus","volume":"77","author":"Kawashima","year":"2000","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11745-007-3129-2","article-title":"Oral administration of dihomo-gamma-linolenic acid prevents development of atopic dermatitis in NC\/Nga mice","volume":"43","author":"Kawashima","year":"2008","journal-title":"Lipids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jdermsci.2015.03.010","article-title":"Dihomo-\u03b3-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC\/Tnd mice","volume":"79","author":"Amagai","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.plefa.2010.02.032","article-title":"Uptake of dihomo-gamma-linolenic acid by murine macrophages increases series-1 prostaglandin release following lipopolysaccharide treatment","volume":"83","author":"Kakutani","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_28","first-page":"239","article-title":"Proceedings: Prostaglandin D1 inhibits the increase in vascular permeability in rat skin produced by prostaglandin E1, E2 and D2","volume":"55","author":"Flower","year":"1975","journal-title":"Br. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/BF00375798","article-title":"Effect of dihomogammalinolenic acid and its 15-lipoxygenase metabolite on eicosanoid metabolism by human mononuclear leukocytes in vitro: Selective inhibition of the 5-lipoxygenase pathway","volume":"284","author":"Iversen","year":"1992","journal-title":"Arch. Dermatol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.4049\/jimmunol.143.4.1303","article-title":"Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism","volume":"143","author":"Santoli","year":"1989","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0952-3278(99)80015-5","article-title":"Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: Effects of unsaturated fatty acids","volume":"60","author":"Zurier","year":"1999","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2332\/allergolint.11-RAI-0334","article-title":"Japanese guideline for allergic rhinitis","volume":"60","author":"Okubo","year":"2011","journal-title":"Allergol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nri1934","article-title":"Immunological mechanisms of allergen-specific immunotherapy","volume":"6","author":"Akdis","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.jaci.2017.03.050","article-title":"Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision","volume":"140","author":"Bousquet","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1111\/jdv.16716","article-title":"European Task Force on Atopic Dermatitis (ETFAD): Treatment targets and treatable traits in atopic dermatitis","volume":"34","author":"Thyssen","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1136\/bmj.2.6100.1441","article-title":"Antithrombotic potential of dihomo-gamma-linolenic acid in man","volume":"2","author":"Kernoff","year":"1977","journal-title":"Br. Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1271\/bbb.90112","article-title":"Oral supplementation with dihomo-gamma-linolenic acid-enriched oil altered serum fatty acids in healthy men","volume":"73","author":"Teraoka","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s11745-012-3664-3","article-title":"Oral supplementation with dihomo-\u03b3-linolenic acid (DGLA)-enriched oil increases serum DGLA content in healthy adults","volume":"47","author":"Tanaka","year":"2012","journal-title":"Lipids"},{"key":"ref_39","unstructured":"NAME Committees (2016). Practical Guideline for the Management of Allergic Rhinitis in Japan, (In Japanese)."},{"key":"ref_40","unstructured":"NAME Committees (2020). Practical Guideline for the Management of Allergic Rhinitis in Japan, (In Japanese)."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1080\/00016480510026944","article-title":"Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires","volume":"125","author":"Okuda","year":"2005","journal-title":"Acta Otolaryngol."},{"key":"ref_42","first-page":"21","article-title":"Standard questionnaire for QOL of Japanese patients with allergic rhinitis","volume":"52","author":"Okuda","year":"2003","journal-title":"Arerugi"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1093\/ajcn\/54.4.668","article-title":"Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: Study design implications","volume":"54","author":"Brown","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1291\/hypres.24.537","article-title":"Effects of eicosapentaenoic acid on blood pressure, cell membrane fatty acids, and intracellular sodium concentration in essential hypertension","volume":"24","author":"Miyajima","year":"2001","journal-title":"Hypertens. Res."},{"key":"ref_45","first-page":"721","article-title":"A novel dietary questionnaire: The Calorie and Nutrition Diary (CAND)","volume":"61","author":"Suzuki","year":"2019","journal-title":"New Food Indust."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/153537020422900305","article-title":"Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans","volume":"229","author":"Takano","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.pharmtox.011008.145616","article-title":"Lipid mediators in health and disease: Enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation","volume":"49","author":"Shimizu","year":"2009","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1080\/09168451.2019.1667220","article-title":"Oral administration of whole dihomo-\u03b3-linolenic acid-producing yeast suppresses allergic contact dermatitis in mice","volume":"84","author":"Watanabe","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1006\/cimm.1994.1158","article-title":"Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes","volume":"156","author":"Yamaoka","year":"1994","journal-title":"Cell Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/1056-8719(93)90058-M","article-title":"In vivo microdialysis measurement of histamine in rat blood effects of compound 48\/80 and histamine receptor antagonists","volume":"29","author":"Sakurai","year":"1993","journal-title":"J. Pharmacol. Toxicol. Methods"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/15\/3465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:26:18Z","timestamp":1760127978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/15\/3465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,5]]},"references-count":50,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["nu15153465"],"URL":"https:\/\/doi.org\/10.3390\/nu15153465","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,5]]}}}