Prevention & lipidsCohort study
Effect of Low-Carbohydrate and Low-Fat Diets on Metabolomic Indices and Coronary Heart Disease in U.S. Individuals
- Prospective cohort study
- 3 pooled cohorts (HPFS, Nurses' Health Study (NHS), NHSII)
Authors' conclusion
These findings highlight the critical role of diet quality in determining health effects of low-carbohydrate and low-fat diets on CHD risk.
Study context
- Population
- US men (HPFS, 1986–2016) and women (NHS, 1986–2018; NHSII, 1991–2019)42,720 men
- Exposure
- Highest vs lowest low-carbohydrate diet (LCD) and low-fat diet (LFD) index scores
- Outcome
- CHD incidence
Main finding
As reported in the abstract
CHD
Hazard ratio (95% CI)
overall LCD
1.05(1.01–1.10)
animal LCD
1.07(1.02–1.12)
vegetable LCD
0.94(0.90–0.99)
unhealthy LCD
1.14(1.09–1.20)
healthy LCD
0.85(0.82–0.89)
overall LFD
0.93(0.89–0.98)
animal LFD
0.94(0.90–0.98)
vegetable LFD
0.87(0.83–0.91)
unhealthy LFD
1.12(1.07–1.17)
healthy LFD
0.87(0.83–0.91)
Observational data: associations, not effects.
Further findings
Biomarkers and metabolomic profiles
- Healthy LCD and LFD linked to lower TG, higher HDL-C, lower hs-CRP, increased 3-indolepropionic acid, decreased valine; unhealthy patterns opposite
Multimetabolite scores of LCD and LFD indices
- Correlation in lifestyle validation studies (LVS) (Spearman r)
- 0.57-0.68
- Replication in NHS, NHSII, HPFS (r)
- 0.21-0.38
- Associations with coronary heart disease (CHD) risk highly consistent with food frequency questionnaire (FFQ)-based
Original publication
Effect of Low-Carbohydrate and Low-Fat Diets on Metabolomic Indices and Coronary Heart Disease in U.S. Individuals. J Am Coll Cardiol. Published 11 February 2026. doi:10.1016/j.jacc.2025.12.038
Summarised from the published abstract; every number is checked against it