Dietary patterns, ceramide ratios, and risk of all-cause and cause-specific mortality: the Framingham offspring study

Authors: WALKER, MAURA - Boston University; XANTHAKIS, VANESSA - Boston University; PETERSON, LINDA - Washington University; DUNCAN, MEREDITH - Vanderbilt University; LEE, JOOWON - Boston University; MA, JIANTAO - Tufts University; BIGORNIA, SHERMAN - University Of New Hampshire; MOORE, LYNN - Boston University; QUATROMONI, PAULA - Boston University; VASAN, RAMACHANDRAN - Boston University; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2020
Publication Date: 9/16/2020
Citation: Walker, M.E., Xanthakis, V., Peterson, L.R., Duncan, M.S., Lee, J., Ma, J., Bigornia, S., Moore, L.L., Quatromoni, P.A., Vasan, R.S., Jacques, P.F. 2020. Dietary patterns, ceramide ratios, and risk of all-cause and cause-specific mortality: the Framingham offspring study. Journal of Nutrition. 150(11):2994-3004. https://doi.org/10.1093/jn/nxaa269.
DOI: https://doi.org/10.1093/jn/nxaa269

Interpretive Summary: Ceramides are a type of lipid found in high concentrations within cell membranes and critical to membrane function. Ceramides are heterogeneous in their hydrocarbon chain length resulting in distinct physiological properties and different relations with risk of diseases such as coronary artery disease, cancer, and Alzheimer disease. As a healthy diet appears to influence ceramide levels in blood, alterations in ceramide metabolism may represent a mechanism by which one may reduce the risk of death related to non-communicable diseases. To address this knowledge gap, the present study sought to determine if complementary dietary patterns, a healthy American dietary pattern and a Mediterranean-style dietary pattern, modified associations between ceramides and risk of all-cause and cause-specific mortality in heathy community dwelling middle-aged adults. We observed that a higher overall diet quality attenuated the association between ceramides and cancer mortality, suggesting that there may be shared biological mechanisms in the relations among ceramides, diet, and cancer mortality.

Technical Abstract: Rationale: Prior evidence suggests that diet is a modifier in the relation of ceramides and ceramide ratios with risk of incident cardiovascular disease (CVD) in high-risk individuals. It remains unknown if diet quality modifies the relations between ceramide ratios and mortality in community-dwelling middle-aged adults. Objective: To examine if healthy dietary patterns modify relations of ceramide ratios with all-cause and cause-specific mortality, and to determine how differing healthy dietary patterns associate with concentrations of circulating ceramides. Methods and Results: We examined 2157 participants of the Framingham Offspring Study (mean age = 66 years, 55% women). The Dietary Guidelines Adherence Index (DGAI) and Mediterranean-style Diet Score (MDS) were derived using semi-quantitative food frequency questionnaires. Ceramides were previously quantified using a validated assay. Over a mean follow-up of 10 years, there were 469 deaths, 101 due to CVD and 172 due to cancer. Consistent with prior work, the C24:0/C16:0 and C22:0/C16:0 ceramide ratios were inversely associated with all-cause and CVD mortality (all P < 0.05). The C24:0/C16:0 and C22:0/C16:0 ceramide ratios were associated with a lower hazard of cancer mortality. Adjusted-multivariable hazard ratios (95% CIs) were 0.75 (0.64, 0.88) and 0.75 (0.65, 0.87), respectively. The associations of the ceramide ratios with all-cause and cancer mortality were modified by overall diet quality (DGAI or MDS, all Pinteraction < 0.1). Inverse associations of the C24:0/C16:0 and C22:0/C16:0 ceramide ratios and cancer mortality were attenuated and became non-significant in individuals with a higher diet quality (DGAI or MDS above the median). Conclusion: A higher overall diet quality attenuates the association between ceramide ratios and cancer mortality in a of population community-dwelling middle-aged adults. These data may suggest shared biological mechanisms in the relations among ceramides, diet, and cancer mortality.