MADRID — At the International Scientific Symposium “New Frontiers of Scientific Research” recently held in Barcelona, specialists analyzed the role of the very low-calorie ketogenic diet. This analysis focused on three comorbidities that have a higher incidence in overweight and obese patients: polycystic ovary syndrome, non-alcoholic fatty liver disease and type 2 diabetes. The experts’ objective? Analyze and update the latest evidence on the benefits of this food choice.
Polycystic ovary syndrome
Alessandra Gambineri, MD, PhD, Associate Professor, Department of Medicine and Surgery (DIMEC), University of Bologna, Bologna, Italy, discussed the link between obesity and polycystic ovary syndrome, which she described as a chronic disease that affects approximately 10% of women of reproductive age and exhibits various phenotypes with different characteristics.
“The pathophysiology of this syndrome is characterized by the interaction of three factors: excess androgens, adipose tissue dysfunction and insulin resistance. These factors interact with each other and are expressed differently in each phenotype,” Gambineri said.
She indicated that adipose tissue dysfunction is at the heart of this pathology. This centrality results from its association with secretions, such as free fatty acids, pro-inflammatory cytokines, certain adipokines which promote insulin resistance, glucocorticoids, androgens and oxidative stress.
“Similarly, the oxidative stress that characterizes this syndrome is increasingly present in obese people,” Gambineri said. “This oxidative stress also produces ovarian hypotoxicity which worsens ovulatory function. In this context, the very low calorie ketogenic diet can be useful in several ways: weight reduction, promotion of mainly visceral / abdominal fat loss, decrease in lipotoxicity , and improvement of inflammation, hyperinsulinemia and insulin resistance.”
This was the path followed to conduct a study to analyze the effects of the very low-calorie ketogenic diet on the manifestations of polycystic ovary syndrome in the obesity phenotype. Gambineri presented his results.
“The goal was to compare the effects of a very low-calorie ketogenic diet and the standard low-calorie (low-calorie) diet as a control group,” she said. “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 resistance to insulin. ‘insulin.”
Study participants had a diagnosis of polycystic ovary syndrome as defined by National Institutes of Health (NIH) criteria and were between the ages of 18 and 45. These women were randomly assigned to two groups of equal size: experimental (very low-calorie ketogenic diet) and control (low-calorie diet). “Women assigned to the experimental group followed the ketogenic stage for eight weeks and then transitioned to the second phase of the low-calorie diet for an additional eight weeks, while those in the control group (low-calorie diet) followed the low-calorie diet for eight weeks. every 16 weeks.”
The primary outcomes were changes in weight and body composition, particularly fat mass and lean mass, measured by bioimpedance. “The observed changes in the following aspects were considered secondary outcomes: abdominal fat distribution, metabolic parameters, ovulation, ovarian morphology, hirsutism, hyperandrogenism, psychological well-being, and psychological distress,” Gambineri said. “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 versus −2.2% in the control group), fat mass (−15.1% versus −8.5 %) and free testosterone (−30.3% versus +10.6%). Only the experimental group saw a reduction in insulin.
“A key point regarding hyperandrogenism, particularly with regard to what is called free testosterone, there was only a significant reduction in the very low calorie ketogenic diet group,” said said Gambineri. “This reduction was particularly 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 the sex hormone binding globulins, SHB6. Said globulins bind to the testosterone present in female blood, producing a reduction in free testosterone, a very significant effect considering that this syndrome is an androgenic disorder.Additionally, current treatments for polycystic ovary syndrome do not reduce free testosterone as much as this dietary approach.
For the specialist, among all these positive effects in these patients, perhaps the most important is the noticeable improvement in ovulation. “At the start of the study, only 38.5% of 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.”
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.”
Reverse type 2 diabetes?
Daniela Sofrà, MD, an endocrinologist specializing in diabetes at Clinique La Source in Lausanne, Switzerland, reviewed the current evidence on the role of the very low-calorie ketogenic diet in the management of type 2 diabetes.
“It’s time to rethink the treatment of diabetes and focus efforts on managing obesity as an associated factor,” she said. “One of the hypotheses examined in this regard is the twin cycle, which posits that type 2 diabetes is the result of excess fat in the liver. This in turn is associated with resistance to insulin with pancreatic dysfunction.”
Sofrà added that there is a study documenting for the first time the reversibility of the morphology of the diabetic pancreas after calorie restriction with the very low calorie ketogenic diet. “The reason for this effect is the use of visceral and intrahepatic fat, which may lead to remission of the clinical manifestation of type 2 diabetes, including as such the definition made by the American Diabetes Association: glycosylated hemoglobin
Specifically, the results of this research showed that after following the very low calorie ketogenic diet and achieving a 15% weight loss (average weight loss of the participants), glucose levels in the liver returned to low levels. normal in 7 days. Beta cell function returned to near normal within 8 weeks.
“Subsequent studies have shown the durability of the remission of type 2 diabetes, thanks to the reactivation of the insulin-secreting function of the beta cells which have become dedifferentiated in the face of the chronic excess of nutrients. In concrete terms, 6 out of 10 patients maintained a glycosylated hemoglobin
Likewise, she pointed out that the likelihood of achieving remission is primarily determined by the duration of the disease. “The years of diabetes are one of the main predictors of the response that the patient will have with this dietary intervention. Studies have shown that remission is possible in patients who have had diabetes for less than 6 years, although there are other projects that indicate that it can be carried out with a duration of up to 10 years.”
Based on these data, Sofrà highlighted the pleiotropic effects of the very low-calorie ketogenic diet on glycemic control, favoring the eventual remission of diabetes or the reduction of medications, as well as the reduction of the HOMA-IR index (resistance to insulin) and waist circumference in people with type 2 diabetes.
Non-alcoholic fatty liver disease
The third comorbidity of obesity that may benefit from the very low-calorie ketogenic diet is fatty liver disease, or non-alcoholic fatty liver disease, said Hardy Walle, MD, internal medicine specialist and director/founder of the Bodymed Center, Kirkel, Germany and a of the authors of this research.
“Recent research shows that ectopic fat and non-alcoholic fatty liver disease could be considered a cause, or at least one of the causes, of most of the diseases that affect the population due to overweight and obesity” , Walle said. “Some authors have stated that without fatty liver there is no type 2 diabetes.”
Walle pointed out that between 30% and 40% of the adult population suffers from non-alcoholic fatty liver disease, a percentage that increases considerably in obese people, reaching 70% prevalence and increasing, in the case of type 2 diabetes, to almost 90%. “Even a normal weight does not exclude fatty liver disease; in fact, about 15% of people with non-alcoholic fatty liver disease are not overweight.”
In a setting where there are no approved drugs for the treatment of fatty liver disease (the current standard approach focuses on lifestyle interventions), a short-term calorie restricted diet (or liver fast) is considered an effective method for the management of this pathology. This principle was demonstrated by a study from Saarland University, Saarbrücken, Germany, which Walle used to illustrate this claim.
“Participants (60 patients with fatty liver disease) followed a low-calorie diet (less than 1000 kcal/day) for 14 days with a protein- and fiber-rich formula specially developed for the treatment of non-alcoholic fatty liver disease. A fibroscan was was then performed with controlled measurement of attenuation parameters to quantify fatty liver disease.Results showed not only a significant improvement in non-alcoholic fatty liver disease parameters, but also a marked improvement in all relevant metabolic parameters (serum lipids, liver enzymes),” Walle explained.
“This evidence leads us to affirm that the concept of hepatic fasting (by means of a low-calorie diet) marks a benchmark for a future therapeutic approach to non-alcoholic fatty liver disease,” he concluded.
The study presented by Gambineri was carried out with the collaboration of the Pronokal group (Nestlé Health Science). Gambineri, Sofrà and Walle disclosed no relevant financial relationship.
This article was translated from Medscape Spanish edition.