Essential Nutrients, Added Sugar Intake, and Epigenetic Age in Midlife Black and White Women: NIMHD Social Epigenomics Program.

Importance: Nutritive compounds play critical roles in DNA replication, maintenance, and repair, and also serve as antioxidant and anti-inflammatory agents. Sufficient dietary intakes support genomic stability and preserve health.

Objective: To investigate the associations of dietary patterns, including intakes of essential nutrients and added sugar, and diet quality scores of established and new nutrient indices with epigenetic age in a diverse cohort of Black and White women at midlife.

Design, setting, and participants: This cross-sectional study included analyses (2021-2023) of past women participants of the 1987-1997 National Heart, Lung, and Blood Institute Growth and Health Study (NGHS), which examined cardiovascular health in a community cohort of Black and White females aged between 9 and 19 years. Of these participants who were recruited between 2015 and 2019 from NGHS's California site, 342 females had valid completed diet and epigenetic assessments. The data were analyzed from October 2021 to November 2023.

Exposure: Diet quality scores of established nutrient indices (Alternate Mediterranean Diet [aMED], Alternate Healthy Eating Index [AHEI]-2010); scores for a novel, a priori-developed Epigenetic Nutrient Index [ENI]; and mean added sugar intake amounts were derived from 3-day food records.

Main outcomes and measures: GrimAge2, a second-generation epigenetic clock marker, was calculated from salivary DNA. Hypotheses were formulated after data collection. Healthier diet indicators were hypothesized to be associated with younger epigenetic age.

Results: A total of 342 women composed the analytic sample (mean [SD] age, 39.2 [1.1] years; 171 [50.0%] Black and 171 [50.0%] White participants). In fully adjusted models, aMED (β, -0.41; 95% CI, -0.69 to -0.13), AHEI-2010 (β, -0.05; 95% CI, -0.08 to -0.01), and ENI (β, -0.17; 95% CI, -0.29 to -0.06) scores, and added sugar intake (β, 0.02; 95% CI, 0.01-0.04) were each significantly associated with GrimAge2 in expected directions. In combined analyses, the aforementioned results with GrimAge2 were preserved with the association estimates for aMED and added sugar intake retaining their statistical significance.

Conclusions and relevance: In this cross-sectional study, independent associations were observed for both healthy diet and added sugar intake with epigenetic age. To our knowledge, these are among the first findings to demonstrate associations between added sugar intake and epigenetic aging using second-generation epigenetic clocks and one of the first to extend analyses to a diverse population of Black and White women at midlife. Promoting diets aligned with chronic disease prevention recommendations and replete with antioxidant or anti-inflammatory and pro-epigenetic health nutrients while emphasizing low added sugar consumption may support slower cellular aging relative to chronological age, although longitudinal analyses are needed.