Background

Sleep is increasingly being viewed as an important determinant of health, and appears to be associated with cardiovascular disease, diabetes and several site-specific cancers. Few epidemiologic studies have used data from a feeding study to explore the impact of sleep habits up on metabolomic profile.

Methods

The Dietary Approaches to Stop Hypertension (DASH)-Sodium feeding trial randomized individuals to either the DASH (low fat, high protein, low-fat dairy and high fruits and vegetables) or control diet (12 weeks) and three levels of sodium intake (30 days each). In a subgroup of 97 participants, we measured the levels of 531 metabolites in serial fasting plasma samples at two time points using liquid chromatography and gas chromatography mass spectrometry. We then assessed the association between each metabolite and sleep using a linear random effects model adjusted for age, sex, race, dietary pattern and sodium level. The resulting p-values were combined using Fisher's method to estimate the association with 38 metabolic pathways.

Data about sleep were collected at the end of two dietary intervention phases. Participants recorded times for going-to-sleep and waking while wearing 24-hour ambulatory blood pressure monitors. From this we produced two sleep variables - sleep mid-point (the median time between going to sleep and waking) and sleep duration. We undertook further analysis to explore the associations between bedtime, wake-time and metabolic pathways and metabolites.

Results

Nineteen pathways were significantly associated (p <0.05) with sleep mid-point, but only the γ-glutamyl amino acid metabolism pathway was associated with sleep mid-point and wake-time at Bonferroni-corrected threshold of 0.0013 (7 individual peptide metabolites contributed and showed positive associations). Fifty-six metabolites were associated with sleep mid-point (FDR<0.20), although none of them reached Bonferroni-corrected significance (p-value <10-5). Notable top metabolites (pathways given in brackets) associated with sleep mid-point and wake-time were CMPF (fatty acid, decarboxylate), erythrulose (an advanced glycation end-product), isovalerate (fatty acid metabolism) and HWESASXX (polypeptide). Neither sleep duration nor bedtime were associated with metabolite pathways or metabolites and there was no significant interaction between sex, race, BMI or dietary intervention and sleep.

Conclusion

Within our study we found multiple metabolites associated with sleep timing. In particular, the γ-glutamyl pathway metabolites were associated with sleep mid-point and wake-time. These metabolites are formed using the enzyme γ-glutamyltransferase (GGT), which is expressed in response to oxidative stress and glutathione synthesis - a process that may play a role in carcinogenesis, diabetes, and cardiovascular disease.

Citation Format: Vanessa L. Gordon-Dseagu, Andriy Derkach, Qian Xiao, Ishmael Williams, Joshua Sampson, Rachael Stolzenberg-Solomon. The association of sleep with metabolic pathways and metabolites: Evidence from the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 380.