Metabolomics-Based Biomarker for Dietary Fat and Associations with Chronic Disease Risk in Postmenopausal Women.

MedStar author(s):
Citation: Journal of Nutrition. 153(9):2651-2662, 2023 09.PMID: 37245660Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Observational Study | Randomized Controlled Trial | Research Support, N.I.H., ExtramuralSubject headings: *Breast Neoplasms | *Coronary Disease | *Diabetes Mellitus | Biomarkers | Breast Neoplasms/ep [Epidemiology] | Carbohydrates | Chronic Disease | Coronary Disease/ep [Epidemiology] | Diet, Fat-Restricted | Dietary Fats | Female | Humans | Postmenopause | Prospective Studies | Risk Factors | United States/ep [Epidemiology] | Women's Health | Year: 2023ISSN:
  • 0022-3166
Name of journal: The Journal of nutritionAbstract: BACKGROUND: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern.CONCLUSIONS: WHI observational data support prior DM trial findings of low-fat dietary pattern benefits in this population of postmenopausal United States women.METHODS: Prospective disease association results are presented using WHI cohorts of postmenopausal women, aged 50-79 y when enrolled at 40 United States clinical centers. Biomarker equations were developed using an embedded human feeding study (n = 153). Calibration equations were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with cancer, cardiovascular diseases, and diabetes incidence in WHI cohorts (n = 81,954) over an approximate 20-y follow-up period.OBJECTIVES: We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts. Corresponding studies for specific fatty acids will follow separately.RESULTS: A biomarker for fat density was developed by subtracting protein, carbohydrate, and alcohol densities from one. A calibration equation was developed for fat density. Hazard ratios (95% confidence intervals) for 20% higher fat density were 1.16 (1.06, 1.27) for breast cancer, 1.13 (1.02, 1.26) for CHD, and 1.19 (1.13, 1.26) for diabetes, in substantial agreement with findings from the DM trial. With control for additional dietary variables, especially fiber, fat density was no longer associated with CHD, with hazard ratio (95% confidence interval) of 1.00 (0.88, 1.13), whereas that for breast cancer was 1.11 (1.00, 1.24).TRIAL REGISTRATION NUMBER: This study is registered with clinicaltrials.gov identifier: NCT00000611. Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.All authors: Prentice RL, Vasan S, Tinker LF, Neuhouser ML, Navarro SL, Raftery D, Gowda GN, Pettinger M, Aragaki AK, Lampe JW, Huang Y, Van Horn L, Manson JE, Wallace R, Mossavar-Rahmani Y, Wactawski-Wende J, Liu S, Snetselaar L, Howard BV, Chlebowski RT, Zheng CFiscal year: FY2024Digital Object Identifier: Date added to catalog: 2023-11-22
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Journal Article MedStar Authors Catalog Article 37245660 Available 37245660

BACKGROUND: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern.

CONCLUSIONS: WHI observational data support prior DM trial findings of low-fat dietary pattern benefits in this population of postmenopausal United States women.

METHODS: Prospective disease association results are presented using WHI cohorts of postmenopausal women, aged 50-79 y when enrolled at 40 United States clinical centers. Biomarker equations were developed using an embedded human feeding study (n = 153). Calibration equations were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with cancer, cardiovascular diseases, and diabetes incidence in WHI cohorts (n = 81,954) over an approximate 20-y follow-up period.

OBJECTIVES: We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts. Corresponding studies for specific fatty acids will follow separately.

RESULTS: A biomarker for fat density was developed by subtracting protein, carbohydrate, and alcohol densities from one. A calibration equation was developed for fat density. Hazard ratios (95% confidence intervals) for 20% higher fat density were 1.16 (1.06, 1.27) for breast cancer, 1.13 (1.02, 1.26) for CHD, and 1.19 (1.13, 1.26) for diabetes, in substantial agreement with findings from the DM trial. With control for additional dietary variables, especially fiber, fat density was no longer associated with CHD, with hazard ratio (95% confidence interval) of 1.00 (0.88, 1.13), whereas that for breast cancer was 1.11 (1.00, 1.24).

TRIAL REGISTRATION NUMBER: This study is registered with clinicaltrials.gov identifier: NCT00000611. Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.

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