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Background <p>Previous findings for the association of fish intake and its related metabolites on risk of metabolic syndrome (MetS) are inconsistent and limited. The prevalence of fish and shellfish consumers are high in Japan where it contributes to one fourth of the protein intake. We aimed to investigate the relationship of fish and fish-related metabolites with MetS risk factors in a community-dwelling Japanese population.</p> Methods <p>In this cross-sectional study, 1047 Japanese men and women aged 40–59&#xa0;years were included. Four in-depth multiple-pass 24-h dietary recalls, two timed 24-h urine collections, blood collection, extensive questionnaire and anthropometric measurements were collected for each participant. Urinary and serum profiles were obtained using <sup>1</sup>H Nuclear magnetic resonance (NMR) spectroscopy.</p> Results <p>Mean fish intake was 47.0 (SD 28.8) g per 1000&#xa0;kcal. Urinary trimethylamine-<i>N</i>-oxide (TMAO) and taurine, and serum creatine and threonine were significantly correlated with fish intake and homarine was associated with shellfish intake (<i>p</i> &lt; 0.01). Significant inverse associations were found between triglycerides and total fish intake, low omega-3 fish, urinary TMAO, taurine and between urinary taurine with systolic blood pressure. Direct association between urinary TMAO and serum threonine with high-density lipoprotein cholesterol were found.</p> Conclusion <p>We found several metabolites related to fish intake and risk factors of MetS in habitual fish-consuming country, Japan. When stratified by seafood type, raw and high omega-3 fish intake showed the strongest associations with urinary and serum metabolomes, while fried fish had weaker or non-significant correlations, suggesting that cooking methods may modulate the bioavailability or metabolic impact of fish nutrients. The combined panel of urinary TMAO and taurine with plasma creatine and threonine, reflecting seafood intake, was associated with a favorable lipid profile and lower blood pressure.</p> Clinical trail registration <p>The INTERMAP study is registered as NCT00005271 at <a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>.</p> Graphical abstract <p></p>

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Association between fish-related metabolites and metabolic syndrome risk factors in Japan: INTERLIPID metabolome –wide association study

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Tserenlkham Byambajav,
  • Queenie Chan,
  • Yukiko Okami,
  • Aya Kadota,
  • Naoko Miyagawa,
  • Nagako Okuda,
  • Hideaki Nakagawa,
  • Kiyomi Sakata,
  • Shigeyuki Saitoh,
  • Akira Okayama,
  • Katsushi Yoshita,
  • Kamal Masaki,
  • Chung-Ho E. Lau,
  • Timothy M. Ebbels,
  • Linda Van Horn,
  • Elaine Holmes,
  • Paul Elliott,
  • Jeremiah Stamler,
  • Hirotsugu Ueshima,
  • Katsuyuki Miura

摘要

Background

Previous findings for the association of fish intake and its related metabolites on risk of metabolic syndrome (MetS) are inconsistent and limited. The prevalence of fish and shellfish consumers are high in Japan where it contributes to one fourth of the protein intake. We aimed to investigate the relationship of fish and fish-related metabolites with MetS risk factors in a community-dwelling Japanese population.

Methods

In this cross-sectional study, 1047 Japanese men and women aged 40–59 years were included. Four in-depth multiple-pass 24-h dietary recalls, two timed 24-h urine collections, blood collection, extensive questionnaire and anthropometric measurements were collected for each participant. Urinary and serum profiles were obtained using 1H Nuclear magnetic resonance (NMR) spectroscopy.

Results

Mean fish intake was 47.0 (SD 28.8) g per 1000 kcal. Urinary trimethylamine-N-oxide (TMAO) and taurine, and serum creatine and threonine were significantly correlated with fish intake and homarine was associated with shellfish intake (p < 0.01). Significant inverse associations were found between triglycerides and total fish intake, low omega-3 fish, urinary TMAO, taurine and between urinary taurine with systolic blood pressure. Direct association between urinary TMAO and serum threonine with high-density lipoprotein cholesterol were found.

Conclusion

We found several metabolites related to fish intake and risk factors of MetS in habitual fish-consuming country, Japan. When stratified by seafood type, raw and high omega-3 fish intake showed the strongest associations with urinary and serum metabolomes, while fried fish had weaker or non-significant correlations, suggesting that cooking methods may modulate the bioavailability or metabolic impact of fish nutrients. The combined panel of urinary TMAO and taurine with plasma creatine and threonine, reflecting seafood intake, was associated with a favorable lipid profile and lower blood pressure.

Clinical trail registration

The INTERMAP study is registered as NCT00005271 at www.clinicaltrials.gov.

Graphical abstract