{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:46:32Z","timestamp":1790739992264,"version":"4.1.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>There is a large heterogeneity in LDL-cholesterol change among individuals adopting ketogenic diets. Interestingly, lean metabolically healthy individuals seem to be particularly susceptible, with an inverse association between body mass index and LDL-cholesterol change. The lipid energy model proposes that, in lean healthy individuals, carbohydrate restriction upregulates systemic lipid trafficking to meet energy demands. To test if anthropometric and energy metabolism markers predict LDL-cholesterol change during carbohydrate restriction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten lean, healthy, premenopausal women who habitually consumed a ketogenic diet for \u22656 months were engaged in a three-phase crossover study consisting of continued nutritional ketosis, suppression of ketosis with carbohydrate reintroduction, and return to nutritional ketosis. Each phase lasted 21 days. The predictive performance of all available relevant variables was evaluated with the linear mixed-effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All body composition metrics, free T<jats:sub>3<\/jats:sub> and total T<jats:sub>4<\/jats:sub>, were significantly associated with LDL-cholesterol change. In an interaction model with BMI and free T<jats:sub>3<\/jats:sub>, both markers were significant independent and interacting predictors of LDL-cholesterol change. Neither saturated fat, HOMA-IR, leptin, adiponectin, TSH, nor rT<jats:sub>3<\/jats:sub> was associated with LDL-cholesterol changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Among lean, healthy women undergoing carbohydrate restriction, body composition and energy metabolism markers are major drivers of LDL-cholesterol change, not saturated fat, consistent with the lipid energy model.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1326768","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T04:50:30Z","timestamp":1703134230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model"],"prefix":"10.3389","volume":"14","author":[{"given":"Isabella D.","family":"Cooper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sanchez-Pizarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G.","family":"Norwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvoni","family":"Kyriakidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurtis","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Petagine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Elliot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Soto-Mota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/14651858.CD001903.pub4","article-title":"Ketogenic diets for drug-resistant epilepsy","volume":"2018","author":"Martin-Mcgill","year":"2018","journal-title":"Cochrane Database Systematic Rev"},{"key":"B2","first-page":"141","article-title":"Ketotherapeutics for neurodegenerative diseases","volume-title":"International review of neurobiology","author":"Norwitz","year":""},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/FPSYT.2022.951376\/BIBTEX","article-title":"The ketogenic diet for refractory mental illness: A retrospective analysis of 31 inpatients","volume":"13","author":"Danan","year":"2022","journal-title":"Front Psychiatry"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1017\/jns.2021.67","article-title":"Restricting carbohydrates and calories in the treatment of type 2 diabetes: A systematic review of the effectiveness of \u201clow-carbohydrate\u201d interventions with differing energy levels","volume-title":"Journal of nutritional science","author":"Nicholas","year":"2021"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/nu13030814","article-title":"A ketogenic low-carbohydrate high-fat diet increases LDL cholesterol in healthy, young, normal-weight women: A randomized controlled feeding trial","volume":"13","author":"Bur\u00e9n","year":"2021","journal-title":"Nutrients"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cdn\/nzab144","article-title":"Elevated LDL cholesterol with a carbohydrate-restricted diet: evidence for a \u201cLean mass hyper-responder\u201d Phenotype","volume":"6","author":"Norwitz","year":"2022","journal-title":"Curr Developments Nutr"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/METABO12050460","article-title":"The lipid energy model: reimagining lipoprotein function in the context of carbohydrate-restricted diets","volume":"12","author":"Norwitz","year":"2022","journal-title":"Metabolites"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS242115621","article-title":"Ketosis suppression and ageing (KetoSAge): the effects of suppressing ketosis in long term keto-adapted non-athletic females","volume":"24","author":"Cooper","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B9","unstructured":""},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.04.004","article-title":"Energy balance regulation by thyroid hormones at central level","volume":"19","author":"L\u00f3pez","year":"2013","journal-title":"Trends Mol Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS160716158","article-title":"Thyroid hormone mediated modulation of energy expenditure","volume":"16","author":"Vaitkus","year":"2015","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0269440","article-title":"Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial","volume":"17","author":"Iacovides","year":"2022","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/CPHY.C150017","article-title":"Euthyroid sick syndrome","volume":"6","author":"Lee","year":"2016","journal-title":"Compr Physiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1970","article-title":"Prolonged glycemic adaptation following transition from a low- to high-carbohydrate diet: A randomized controlled feeding trial","volume":"45","author":"Jansen","year":"2022","journal-title":"Diabetes Care"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1326768\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T04:50:32Z","timestamp":1703134232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1326768\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":14,"alternative-id":["10.3389\/fendo.2023.1326768"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1326768","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]},"article-number":"1326768"}}