{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:41:53Z","timestamp":1790606513256,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AT005295"],"award-info":[{"award-number":["R01AT005295"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We used an LC-MS\/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as \u201c1-amino d-proline\u201d) induced at least 15-fold elevated plasma cystathionine. Surprisingly, plasma homocysteine (Hcy) was stable in flaxseed-fed hens despite such highly elevated cystathionine. To explain stable Hcy, our data suggest accelerated Hcy remethylation via BHMT and MS-B12. Also supporting accelerated Hcy remethylation, we observed elevated S-adenosylmethionine (SAM), an elevated SAM:SAH ratio, and elevated methylthioadenosine (MTA), in flaxseed-fed hens. These results suggest that flaxseed increases SAM biosynthesis and possibly increases polyamine biosynthesis. The following endpoint phenotypes were observed in hens consuming flaxseed: decreased physiological aging, increased empirical lifespan, 9\u201314% reduced body mass, and improved liver function. Overall, we suggest that flaxseed can protect women from ovarian tumor metastasis by decreasing omental adiposity. We also propose that flaxseed protects cancer patients from cancer-associated cachexia by enhancing liver function.<\/jats:p>","DOI":"10.3390\/molecules26185674","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T22:34:01Z","timestamp":1632263641000},"page":"5674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Flaxseed Increases Animal Lifespan and Reduces Ovarian Cancer Severity by Toxically Augmenting One-Carbon Metabolism"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-6919","authenticated-orcid":false,"given":"William C.","family":"Weston","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular & Systemic Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-7691","authenticated-orcid":false,"given":"Karen H.","family":"Hales","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale B.","family":"Hales","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular & Systemic Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA"},{"name":"Department of Obstetrics & Gynecology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/IGC.0b013e3181a41613","article-title":"Histopathology of ovarian tumors in laying hens, a preclinical model of human ovarian cancer","volume":"19","author":"Barua","year":"2009","journal-title":"Int. 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