Very Low-calorie Ketogenic Diet Rapidly Augments Testosterone Levels in Non-diabetic Obese Subjects

Background: The very low-calorie ketogenic diet (VLCKD) represents an opportunity to attain clinically relevant weight loss in obese patients. Functional hypogonadism represents a frequent hormonal disorder associated with obesity and visceral fat accumulation characterised by low testosterone levels and subnormal luteinising hormone (LH) levels.

Aim: To evaluate the early effects of VLCKD on serum total testosterone (TT) levels in non-diabetic obese patients.

Methods: Twenty-two obese male patients (mean age 39.3 ± 11.7 years, mean body mass index (BMI) 38.2 ± 6.4 kg/m ) were enrolled and treated for 28 days with VLCKD. Anthropometric and hormonal variables were assessed before, during and after diet intervention.

Results: After 7 and 28 days on a VLCKD, a significant and persistent reduction in body weight, BMI, fat mass, blood glucose, insulin and homeostasis model assessment index was observed compared with baseline. TT significantly increased after 7 days (+35 ± 64 ng/dl) and 28 days (+74 ± 97 ng/dl) on a VLCKD. In addition to TT, a significant increase in serum sex hormone-binding globulin levels was observed after 7 (+2.1 ± 4.1) and 28 days (+7.7 ± 10.0). However, both calculated free testosterone and LH did not change after 7 or 28 days of VLCKD. Following cessation of VLCKD, hypogonadal subjects achieved a higher percentage of total weight loss (8.5% ± 1.5%), a greater reduction in weight (-9.94 ± 1.66 kg), fat mass (-7 ± 2.1 kg) and waist circumference (-6.31 ± 2.65 cm) and a greater improvement in glycaemia (-8.75 ± 10.92 mg/dl) as compared with eugonadal subjects. Furthermore, hypogonadal subjects exhibited a trend of higher TT increase (+98.12 ± 71.51 ng/dl) as compared with eugonadal subjects.

Conclusions: VLCKD results in rapid improvements in TT levels associated with weight loss in male obese non-diabetic subjects, particularly in the presence of obesity-related hypogonadism.