{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:47:10Z","timestamp":1790632030211,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MINISTRY OF HIGHER EDUCATION (MOHE) MALAY SIA","award":["FRGS\/1\/2019\/WAB01\/UIAM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2019\/WAB01\/UIAM\/02\/5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Vitamin B12, only found naturally in animal-based foods, is essential for brain functions and various chemical reactions in the human body. Insufficient vitamin B12 leads to vitamin B12 deficiency, common among strict vegetarians due to their limited intake of animal-based foods. Nevertheless, extensive studies have demonstrated that macroalgae, specifically the Ulva lactuca species, are rich in vitamin B12 and could be further exploited in future dietary applications. In the current study, the ideal extraction method of vitamin B12 from dried U. lactuca was developed and optimised to achieve the maximum vitamin B12 yield. The effects of several extraction parameters, including the solvent-to-solvent, methanol:water (MeOH:H2O), and solute-to-solvent ratios, and pH on the total vitamin B12 content were analysed through a two-level factorial and central composite design. The highest vitamin B12 content, particularly cyanocobalamin (CN-Cbl), was recovered through the ultrasonic-assisted extraction (UAE) of oven-dried U. lactuca at 3 g:60 mL of solute-to-solvent and 25:75% of MeOH to H2O ratios at pH 4. The extraction of CN-Cbl from oven-dried U. lactuca that employed the UAE method has elevated CN-Cbl content recovery compared to other extraction methods.<\/jats:p>","DOI":"10.3390\/molecules27144459","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T20:52:41Z","timestamp":1657659161000},"page":"4459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Optimisation of Vitamin B12 Extraction from Green Edible Seaweed (Ulva lactuca) by Applying the Central Composite Design"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-1150","authenticated-orcid":false,"given":"Deny","family":"Susanti","sequence":"first","affiliation":[{"name":"Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"},{"name":"Sustainable Chemistry Research Group (SusChemRG), Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatin Shazwani","family":"Ruslan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8312-0371","authenticated-orcid":false,"given":"Muhammad Idham","family":"Shukor","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normawaty Mohammad","family":"Nor","sequence":"additional","affiliation":[{"name":"Department of Marine Science, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Iman","family":"Aminudin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"},{"name":"Sustainable Chemistry Research Group (SusChemRG), Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-3090","authenticated-orcid":false,"given":"Muhamad","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Malaysia"},{"name":"Pharmaceutics and Drug Translational Research Group, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junaidi","family":"Khotib","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Anaemia and Cognitive Function among Chinese Elderly in Old Folks Homes","volume":"3","author":"Shahar","year":"2005","journal-title":"J. Sains Kesihat. Malaysia Malays. J. Health Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.clnu.2018.02.008","article-title":"Effect of Two Different Sublingual Dosages of Vitamin B12 on Cobalamin Nutritional Status in Vegans and Vegetarians with a Marginal Deficiency: A Randomized","volume":"38","author":"Riso","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_3","first-page":"155","article-title":"Vitamin B12 Deficiency in the Elderly: Is It Worth Screening","volume":"21","author":"Wong","year":"2015","journal-title":"Hong Kong Med. J."},{"key":"ref_4","first-page":"384","article-title":"Vitamin B12 Deficiency: Recognition and Management","volume":"96","author":"Langan","year":"2017","journal-title":"Am. Fam. Physician"},{"key":"ref_5","unstructured":"National Center for Biotechnology Information (2022, July 11). PubChem Compound Summary for CID 5311498, Cyanocobalamin, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Cyanocobalamin."},{"key":"ref_6","unstructured":"Jayasinghe, P.S., Pahalawattaarachchi, V., and Ranaweera, K.K.D.S. (2022, May 10). Seaweed Based Jam as a Source of Nutrition. Available online: https:\/\/scholar.google.com\/scholar?cluster=6002363050367060791&hl=en&as_sdt=0,5."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fshw.2019.08.001","article-title":"Seaweed Nutraceuticals and Their Therapeutic Role in Disease Prevention","volume":"8","author":"Ganesan","year":"2019","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115852","DOI":"10.1016\/j.carbpol.2020.115852","article-title":"Composition and Structure of Cell Wall Ulvans Recovered from Ulva Spp. along the Swedish West Coast","volume":"233","author":"Nylander","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_9","first-page":"140","article-title":"Ulva Lactuca and Its Polysaccharides: Food and Biomedical Aspects","volume":"6","author":"Mahmood","year":"2016","journal-title":"J. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1753-4887.2007.tb00278.x","article-title":"Nutritional Value of Edible Seaweeds","volume":"65","author":"Macartain","year":"2007","journal-title":"Nutr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijmst.2013.04.009","article-title":"Modeling and Process Optimization for Microbial Desulfurization of Coal by Using a Two-Level Full Factorial Design","volume":"23","author":"Golshani","year":"2013","journal-title":"Int. J. Min. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cej.2010.03.015","article-title":"Process Optimization of Adsorption of Cr (VI) on Activated Carbons Prepared from Plant Precursors by a Two-Level Full Factorial Design","volume":"160","author":"Gottipati","year":"2020","journal-title":"Chem. Eng. J."},{"key":"ref_13","first-page":"1","article-title":"Enhanced Vitamin B12 Production Using Chlorella Vulgaris","volume":"32","author":"Jalilian","year":"2019","journal-title":"Int. J. Eng. Trans. A Basics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4172\/2153-2435.1000337","article-title":"Effect of Different Extraction Methods on Vitamin B12 from Blue Green Algae, Spirulina Platensis","volume":"6","author":"Kumudha","year":"2015","journal-title":"Pharm. Anal. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e03059","DOI":"10.1016\/j.heliyon.2019.e03059","article-title":"The Efficiency of Ultrasonic-Assisted Extraction of Cyanocobalamin Is Greater than Heat Extraction","volume":"6","author":"Xu","year":"2020","journal-title":"Heliyon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1007\/s10811-017-1162-y","article-title":"Optimisation of Ultrasound-Assisted Extraction Conditions for Phenolic Content and Antioxidant Activities of the Alga Hormosira Banksii Using Response Surface Methodology","volume":"29","author":"Dang","year":"2017","journal-title":"J. Appl. Phycol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1007\/s10811-020-02355-2","article-title":"Evaluation of Drying Methods on Nutritional Constituents and Antioxidant Activities of Chlorella Vulgaris Cultivated in an Outdoor Open Raceway Pond","volume":"33","author":"Madhubalaji","year":"2021","journal-title":"J. Appl. Phycol."},{"key":"ref_18","first-page":"3","article-title":"A Review on the Extraction Methods Use in Medicinal Plants, Principle, Strength and Limitation","volume":"4","author":"Azwanida","year":"2015","journal-title":"Med. Aromat. Plants"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.3390\/nu6051861","article-title":"Vitamin B12-Containing Plant Food Sources for Vegetarians","volume":"6","author":"Watanabe","year":"2014","journal-title":"Nutrients"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1080\/01496395.2020.1845208","article-title":"Optimization of Supercritical Fluid Extraction of Asiaticoside from Centella Asiatica Using Central Composite Design (CCD)","volume":"56","author":"Ruslan","year":"2021","journal-title":"Sep. Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1021\/jf504220e","article-title":"Impact of Enzyme- and Ultrasound-Assisted Extraction Methods on Biological Properties of Red, Brown, and Green Seaweeds from the Central West Coast of Portugal","volume":"63","author":"Rodrigues","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ciko, A.M., Joki\u0107, S., \u0160ubari\u0107, D., and Jerkovi\u0107, I. (2018). Overview on the Application of Modern Methods for the Extraction of Bioactive Compounds from Marine Macroalgae. Mar. Drugs, 16.","DOI":"10.3390\/md16100348"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Silva, A.F.R., Abreu, H., Silva, A.M.S., and Cardoso, S.M. (2019). Effect of Oven-Drying on the Recovery of Valuable Compounds from Ulva Rigida, Gracilaria Sp. and Fucus Vesiculosus. Mar. Drugs, 17.","DOI":"10.3390\/md17020090"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.cclet.2009.06.030","article-title":"Use of Packed-Fiber Solid-Phase Extraction for Sample Clean-up and Preconcentration of Vitamin B12 before Determination","volume":"20","author":"Fang","year":"2009","journal-title":"Chinese Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G18","DOI":"10.1149\/2.1471714jes","article-title":"Critical Review\u2014Electrochemical Properties of 13 Vitamins: A Critical Review and Assessment","volume":"165","author":"Lovander","year":"2018","journal-title":"J. Electrochem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109800","DOI":"10.1016\/j.jfoodeng.2019.109800","article-title":"Degradation Kinetics of Vitamin B12 in Model Systems of Different PH and Extrapolation to Carrot and Lime Juices","volume":"272","author":"Bajaj","year":"2020","journal-title":"J. Food Eng."},{"key":"ref_27","first-page":"3","article-title":"No Title","volume":"1","author":"House","year":"2020","journal-title":"Single-Laboratory Valid. AOAC."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijpharm.2006.12.044","article-title":"Stability of Cyanocobalamin in Sugar-Coated Tablets","volume":"337","author":"Ohmori","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3177\/jnsv.58.438","article-title":"Characterization of Vitamin B12 Compounds in the Wild Edible Mushrooms Black Trumpet (Craterellus Cornucopioides) and Golden Chanterelle (Cantharellus Cibarius)","volume":"58","author":"Watanabe","year":"2012","journal-title":"J. Nutr. Sci. Vitaminol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:49:02Z","timestamp":1760140142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,12]]},"references-count":29,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27144459"],"URL":"https:\/\/doi.org\/10.3390\/molecules27144459","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,12]]}}}