Despite numerous observational and experimental studies, the relationship between types of dietary fat and certain chronic degenerative diseases remains unclear. For example, some studies have concluded that omega-6 fatty acids are associated with lower coronary heart disease risk whereas other studies have found no association between specific fatty acids and coronary heart disease risk. These inconsistencies are largely attributed to a lack of objective measures of actual fatty acid intakes.

To better understand these associations, Ross Prentice (Fred Hutchinson Cancer Center; University of Washington) and colleagues conducted a study, published in The Journal of Nutrition, to develop metabolomic biomarkers for fatty acid intake and biomarker-calibrated fatty acid associations with chronic disease risk in postmenopausal women.

The research team used biomarkers derived primarily from blood and urine collected from the Women’s Health Initiative, a long-term national health study that was launched to understand how certain diseases affect post-menopausal women. Participants, between 50-79 years of age, were enrolled at 40 clinical centers throughout the United States. The study included a follow-up period of approximately 20 years. Biomarker equations were based on metabolic values from the Women’s Health Initiative feeding study. Biomarker-calibrated intakes were assessed in relation to disease incidence in a larger Women’s Health Initiative cohort.

Based on unique chemical metabolites associated with selected chronic degenerative diseases, biomarkers were insensitive to trans fatty acid intake. Calibration equations were developed for saturated and polyunsaturated fatty acid density, but not for monosaturated fatty acid density. With or without biomarker calibration, saturated fatty acid density was associated positively with risk of cardiovascular disease, cancer, and type 2 diabetes, although cardiovascular associations were not statistically significant after controlling for other variables, including trans fatty acids and fiber intake. Following this same control, polyunsaturated fatty acid density was not significantly associated with cardiovascular risk, but there were positive associations for some cancers and type 2 diabetes, with or without biomarker calibration.

In this study, corresponding biomarker-calibrated association analyses provided evidence that diets high in saturated fat and polyunsaturated fat may have small adverse associations with certain invasive cancers and type 2 diabetes in postmenopausal United States women.  Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components.


Prentice RL, Vasan S, Tinker LF, Neuhouser ML, Navarro SL, Raftery D, Nagana Gowda GA, Pettinger M, Aragaki AK, Lampe JW, Huang Y, Van Horn L, Manson JE, Wallace RB, Mossavar-Rahmani Y, Wactawski-Wende J, Liu S, Snetselaar L, Howard BV, Chlebowski RT, Zheng C. Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women. The Journal of Nutrition, Volume 153, Issue 9, September 2023, Pages 2663-2677,

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