Environment-wide association study to comprehensively test and validate associations between nutrition and lifestyle factors and testosterone deficiency: NHANES 1988–1994 and 1999–2004

Purpose: Testosterone (T) plays an important role in men’s health and its deficiency is linked with poorer health. However, the role of nutritional and lifestyle factors in T regulation and production remains unclear. The objectives are to comprehensively test the cross-sectional associations of nutritional and lifestyle factors with T deficiency and to validate the associations in the NHANES survey. Methods: We performed weighted multivariable logistic regression analysis to examine the association of 173 nutritional and lifestyle factors with T deficiency (total testosterone ≤ 3.5 ng/mL) in NHANES III as the discovery set (mean age 41). We controlled for multiple comparisons with a false discovery rate (FDR) < 5% and replicated in NHANES 1999–2004 (mean age 44). Results: We identified seven nutritional factors as being inversely associated with T deficiency in NHANES 1999–2004, namely dietary intake of vitamin A, protein, saturated fatty acids, monounsaturated fatty acids, total fats, saturated fatty acid 16:0, and phosphorus. In a multivariable model, only vitamin A intake remained significantly associated with T deficiency (OR 0.97, 95% CI 0.94–0.99). Principal component analysis suggested that the two principal components, (1) dietary fats, protein, and phosphorous and (2) total vitamin A, may be associated with T deficiency. Conclusion: Our systematic evaluation provided new insight into the modifiable factors that could play a role in the regulation of T production. This study has the potential to contribute to the current body of literature which seeks to formulate a clinical definition of T deficiency after taking into account nutritional and lifestyle factors.