MADRID – During the International Scientific Symposium “New Frontiers in Scientific Research” that recently took place in Barcelona, specialists analyzed the role of the very-low-calorie ketogenic diet. This analysis was in relation to three comorbidities that have a higher incidence among overweight and obese patients: polycystic ovary syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. The experts’ aim? To analyze and update the latest evidence on the benefits of this dietary choice.
Polycystic ovary syndrome
Alessandra Gambineri, MD, PhD, associate professor at the department of medicine and surgery (DIMEC) at the University of Bologna, Italy, addressed the link between obesity and polycystic ovary syndrome, which she described as a chronic disease that affects about 10% of women of childbearing age and that presents diverse phenotypes with different characteristics.
“The pathophysiology of this syndrome is characterized by the interaction of three factors: androgen excess, adipose tissue dysfunction, and insulin resistance. These factors interact with each other and are expressed differently in each phenotype,” said Dr. Gambineri.
She indicated that adipose tissue dysfunction is central to this pathology. This centrality results from its association with secretions, such as free fatty acids, proinflammatory cytokines, certain adipokines that promote insulin resistance, glucocorticosteroids, androgens, and oxidative stress.
“Similarly, the oxidative stress that characterizes this syndrome is increasingly present in obese individuals,” said Dr. Gambineri. “This oxidative stress also produces ovary hypotoxicity that aggravates ovulatory function. In this context, the very-low-calorie ketogenic diet can be useful in several ways: weight reduction; promoting the loss of mainly visceral/abdominal fat; decreasing lipotoxicity; and improving inflammation, hyperinsulinemia, and insulin resistance.”
This was the path followed to carry out a study that aimed to analyze the effects of the very-low-calorie ketogenic diet on manifestations of polycystic ovary syndrome in the obesity phenotype. Dr. Gambineri presented its results.
“The objective was to compare the effects of a very-low-calorie ketogenic diet and the standard low-calorie (hypocaloric) diet as a control group,” she said. “The effects studied include body weight, insulin resistance, menstrual cycle, ovulation, ovarian morphology, and hyperandrogenism in a population of 30 obese women with polycystic ovary syndrome and insulin resistance.”
Study participants had a diagnosis of polycystic ovary syndrome as defined by the National Institutes of Health criteria and were aged 18-45 years. These women were randomly assigned to two groups of equal size: experimental (very-low-calorie ketogenic diet) and control (hypocaloric diet). “The women assigned to the experimental group followed the ketogenic stage for eight weeks and then moved to the second, low-calorie diet phase for an additional eight weeks, while those in the control group (hypocaloric diet) followed the low-calorie diet for all 16 weeks.”
The primary outcomes were changes in weight and body composition, specifically fat mass and lean mass, measured by bioimpedance. “The changes observed in the following aspects were considered secondary outcomes: abdominal fat distribution, metabolic parameters, ovulation, ovarian morphology, hirsutism, hyperandrogenism, psychological well-being, and psychological distress,” said Dr. Gambineri. “Any reduction in the ovarian stroma, the area where androgens are synthesized, was also analyzed.”
The study authors found that although BMI decreased in both groups, this reduction was greater in the group that followed the very-low-calorie ketogenic diet. Significant weight loss was observed in both groups, 12.4 kg versus 4.7 kg. Significant differences were also observed in waist circumference (−8.1% in the experimental group vs. −2.2% in the control group), fat mass (−15.1% vs. −8.5%), and free testosterone (−30.3% vs. +10.6%). Only the experimental group saw a reduction in insulin.
“A key point regarding hyperandrogenism, especially regarding what’s referred to as free testosterone, there was only a significant reduction in the very-low-calorie ketogenic diet group,” said Dr. Gambineri. “This reduction was especially evident in the first part of the study, coinciding with the ketogenic period. The reason for this effect lies in the significant increase in the concentration of sex hormone-binding globulins, SHB6. Said globulins bind to the testosterone present in female blood, producing a reduction in free testosterone, a very important effect considering that this syndrome is an androgenic disorder. Furthermore, current treatments for polycystic ovary syndrome do not reduce free testosterone as much as this dietary approach does.”
For the specialist, among all these positive effects in these patients, perhaps most important is the notable improvement that occurs in ovulation. “At the beginning of the study, only 38.5% of the participants in the experimental group and 14.3% of those in the control group had ovulatory cycles. After the intervention, 84.6% managed to ovulate, compared to 35.7% who achieved this goal in the other group.”
Dr. Gambineri suggested that this method is “valid for reducing fat mass and rapidly improving hyperandrogenism and ovulatory dysfunction in women with obesity and polycystic ovary syndrome.”