{
  "abstract": "Micronutrient adequacy, beyond macronutrient balance, may matter for health, yet the effects of low-carbohydrate, high-fat (LCHF) diets on obesity remain unclear. This exploratory three-arm, single-blind randomized controlled trial (N = 300) compared, over 4 weeks, meals optimized to the Japanese Dietary Reference Intakes (DRI; Opti meals, matched macronutrient ratio and 26 micronutrients), a micronutrient-insufficient control diet, and LCHF Opti meals (lower carbohydrate–fat ratio, identical micronutrients). In this partial report, primary outcomes were visceral fat area and salivary cortisol/melatonin, the device-derived streams of that set being reported separately; prespecified secondary outcomes were LDL-cholesterol, systolic/diastolic blood pressure (SBP/DBP), gut microbiota, serum metabolome, and DNA-methylation (DNAm) epigenetic age, analyzed in an exploratory, hypothesis-generating manner. Neither primary outcome differed between groups. LDL-cholesterol decreased in both Opti and LCHF Opti groups versus control, and SBP in the LCHF Opti group. Exploratory analyses showed shifts in gut microbiota and metabolites. In a small subgroup of older male participants (n = 10 per group), the Opti group showed lower PhenoAge, a DNA-methylation measure of biological age linked to mortality risk. Post-hoc machine learning predicted cardiometabolic responders (ROC-AUC 0.71–0.76). DRI-based meals did not outperform the comparators on the primary endpoints; the secondary findings are hypothesis-generating and require confirmation. Clinical Trial Registry number: UMIN000050103, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000056407 (approval: 23/1/2023).",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Akihito Hishikawa"
    },
    {
      "name": "Shintaro Fujii"
    },
    {
      "name": "Jun Iimura"
    },
    {
      "name": "Naohisa Shobako"
    },
    {
      "name": "Takuo Nakazeko"
    },
    {
      "name": "Yukio Hirano"
    },
    {
      "name": "Futoshi Nakamura"
    },
    {
      "name": "Masahiro Yagihashi"
    },
    {
      "name": "Atsushi Nakajima"
    },
    {
      "name": "Yoshinori Katsumata"
    },
    {
      "name": "Kenichiro Kinouchi"
    },
    {
      "name": "Jun Yoshino"
    },
    {
      "name": "Junichiro Irie"
    },
    {
      "name": "Kaori Hayashi"
    },
    {
      "name": "Hiroshi Itoh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2n0jswzgdjx2w.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-73421-x",
  "fulltext_url": null,
  "id": "2n0jswzgdjx2w",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-73421-x",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Diet and metabolism studies"
    ]
  ],
  "openalex": "W7218720677",
  "pdf_url": "https://www.nature.com/articles/s41598-026-73421-x_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-03",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/2n0jswzgdjx2w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.1038/s41598-026-73421-x",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-73421-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Diet and metabolism studies",
      "subfield": "physiology"
    }
  ],
  "title": "Optimized Nutri-Dense meals versus a low-carbohydrate high-fat diet: an exploratory randomized controlled trial",
  "title_text": "Optimized Nutri-Dense meals versus a low-carbohydrate high-fat diet: an exploratory randomized controlled trial",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/2n0jswzgdjx2w",
  "venue": "Scientific Reports",
  "versions": []
}