Ketogenic state is able to improve testosterone serum levels - a meta-analytic approach

Background: It is widely demonstrated that obesity and hypogonadism are bi-directionally correlated, since the hypogonadism prevalence is higher in obese population, while weight loss increases testosterone serum levels. Several approaches are available to contrast weight excess, from simple dietary regimens to more complex surgical procedures. Ketogenic diets (KD) fit in this context and their application is growing year after year, aiming to improve the metabolic and weight patterns in obese patients. However, KD influence on testosterone levels is still poorly investigated. Objectives: To systematically evaluate the potential effect of KD on testosterone levels. Methods: A literature search was performed until April 2022 including studies investigating testosterone levels before and after KD. Secondary endpoints were body weight, estradiol and sex hormone binding globulin serum levels. Any kind of KD was considered eligible, and no specific criteria for study populations were provided. Results: Seven studies (including eight trials) were included in the analysis, five using normocaloric KD and three very low calories KD (VLCKD). Only three studies enrolled overweight/obese men. A significant total testosterone increase was recorded after any kind of KD considering 111 patients (2.86 [0.95, 4.77], P = 0.003). This increase was more evident considering VLCKD compared to normocaloric KD (6.75 [3.31, 10.20], P < 0.001, vs 0.98 [0.08, 1.88], P = 0.030). Meta-regression analyses highlighted significant correlations between the post-KD testosterone raise with patients’ age (R-squared 36.4, P < 0.001) and weight loss (R-squared 73.6, P < 0.001). Conclusions: Comprehensively, KD improved testosterone levels depending on both patients’ age and KD-induced weight loss. However, the lack of information in included studies on hormones of the hypothalamic-pituitary-gonadal axis prevents an exhaustive comprehension about mechanisms connecting ketosis and testosterone homeostasis.