Abstract

Introduction: Increased levels of circulating nitrates were associated with both beneficial and adverse health outcomes in observational and intervention studies. Although more experimental studies are needed to study the underlying mechanisms, it is important to determine the association between multiple dietary and lifestyle factors and circulating nitrates in observation studies to help understand the complicated relationships between circulating nitrates and disease outcomes.

Objective: We plan to determine the associations of red meat, renal function, race, gender, and other lifestyle factors with circulating (urinary and plasma) nitrates.

Methods: Using a cross-sectional design, we analyzed data collected from 5,058 adults (men and women) in the National Health and Nutrition Examination Survey (NHANES) and from 1,260 men in the Health Professionals Follow-up Study (HPFS). Urinary nitrates were measured in the NHANES, and plasma nitrates were measured in the HPFS.

Results: We found an inverse association between unprocessed red meat and circulating (plasma and urinary) nitrates across two studies (NHANES and HPFS) (p for trend <0.001). Furthermore, this inverse association was stronger among participants who had reduced renal functions than participants with normal renal functions in the NHANES and stronger in men who developed prostate cancer later than men who did not develop prostate cancer in the HPFS (p<0.001 for each comparison). Moreover, African Americans had the lowest urinary nitrates among all ethnic groups. Female gender, estimated glomerular filtration rate, age, physical activity, and smoking are positively associated with urinary nitrates whereas urine albumin/creatinine ratio, body mass index, and diabetes were inversely associated with urinary nitrates. P-values are <0.05 for all of these associations. Most associations found in NHANES were similar to those found in HPFS.

Conclusions: We identified new associations of red meat, and reduced renal function with circulating nitrates and confirmed the associations of other lifestyle factors with circulating nitrates identified in previous studies. Our comprehensive analyses helped identify potential confounding factors, can contribute to generating new hypotheses related to factors influencing circulating nitrates, and offer important implications for individualized nutrition.

Keywords: Urinary nitrate; Plasma nitrate; Diet and lifestyle; Biomarker; Red meat; White meat