The ketogenic diet: a co-therapy in the treatment of mood disorders and obesity - a case report


 
 Introduction: There has been a growing interest in the ketogenic diet (KD) due to its suggested therapeutic potential to support numerous chronic diseases. KD is characterized by high amounts of fats and a reduced amount of carbohydrates and protein intake. During following the nutrition protocol, ketones are synthesised, which are the primary source of energy. The elevated concentration of ketones in blood serum inhibits hunger, what leads to reduced body weight. Some authors suggest KD has antidepressant potential and could stabilise mood by affecting neurotransmitters homeostasis in the central nervous system.
 
 Material and methods: The aim of the study was to assess the effect of KD on body weight reduction and improvement of mood in the patients with mood disorder diagnosis. To interpret the results of nutritional intervention, the laboratory parameters and structuralised scales and questionnaires were used.
 
 Results: After following 4-week therapy, the reduction of body weight, correction of some laboratory measurements and reduction in mood symptoms were noticed.
 
 Conclusions: The ketogenic diet affects the anthropometric measurements. However, a variety of simultaneous therapeutic approaches makes impossible determination of the effect on depressive symptoms.


Introduction
Since 1970, the prevalence of obesity has more than tripled worldwide. It is predicted that the number of individuals with overweight and obesity could rise to 38% and 20% respectively in adults population up to the 2030s. The prevalence of obesity can be as high as 85% in the USA in 2030 [1].
Obesity is a significant risk factor for chronic diseases and a cause of premature death. Cardiovascular diseases, type 2 diabetes, malignant neoplasms, depression, chronic kidney disease and liver disease appear most frequently in its course [2].
The epidemic of obesity and motivation to reduced body weight to recommended values affect rising interest in alternative dietary patterns.
One of the strategies that allow quick bodyweight reduction is a diet with high-fat and low-carbohydrates content (VLCKD -Very Low -Carbohydrate Ketogenic Diet, ketogenic diet: DK). The KD has been used in the therapy of drug-resistance epilepsy for a century [3]. Some studies suggest KD could be helpful as a co-treatment of respiratory and cardiovascular diseases [4].
The mechanism of KD is based on stimulation of hepatic synthesis of ketones [5], which is an effect of cutoff carbohydrates intake under 10% of daily requirements of energy [6]. The metabolic consequence is shift in energy source from glycolysis to ketogenesis via directs metabolic reaction towards fatty acids or amino acids oxidation. The result is a synthesis of organic compounds named ketones [5]. Acetoacetate, beta-hydroxybutyrate and acetone are the most frequently characterized ketones.
The condition in which the main source of energy are fats is named "ketosis" and in a metabolic way is similar to changes observed during starvation [6]. The nutritional ketosis called "physiological" is characterized by a concentration of ketones between 0.5 and 3 mg/ dl [7], compared to 30 to 150 mg/dl in acidoketosis [8,9]. Ketogenic diet leads to "physiological" ketosis and excessive glucose concentration of blood not occurring (what is observed in ketoacidosis: < 250 mg/dl) [10]. Acetoacetate and beta-hydroxybutyrate are the primary sources used as alternative energy sources in targeted tissues when glucose levels in blood and glycogen in hepatocytes are insufficient [5]. KD inhibits appetite and evokes the feeling of satiety. DK is recommended to obese and overweight people, including binge eating and food addiction [4,11].
The proposed nutritional protocol of KD is based on the reduction of carbohydrates (<20-50 g/daily) and protein (1-1.5 g/kilogram of body weight/daily) and replacing them with sources of fat [7]. The recommended length of following the diet is from 2-3 weeks up to 6-12 months [12].
Additional to favourable effect of body weight reduction and chronic disease, KD could also positively affect mood. Thus, there is suggested potency of diet as an additional therapy to medication in depression [13]. Some reports confirm the efficacy of the protocol in obesity treatment when it is coexisting with mood disorder [14,15].
In the studies, a relationship between depression and GABA-ergic system deficits was observed. GABA (gamma-aminobutyric acid) is a neurotransmitter that affects the inhibition of central nervous system cells. GABA-ergic neurons regulate neuronal systems transmission, including monoaminergic and cholinergic projection from monoaminergic and cholinergic forebrain. GABA affect CNS via activation of ionotropic receptors GABA A and metabotropic receptors GABA B. The GABA A receptors are known to control and alleviate anxiety potent. In patients suffering from mood disorders, low levels of brain GABA was observed. There are hypotheses that dysfunction of the GABA-ergic system is one of the action target antidepressant treatments [16]. So on, KD could be considered an intervention that strengthens pharmacological treatment of drug-resistant depression [13].
The aim of the study is a case report of patients hospitalized due to depressive disorders and comorbid obesity in. The KD was used as an adjunct to the therapy.

Study case and description
A 21-year-old female, miss, childless with family relations-related problems. Father is an alcohol abuse, and mother is treated for depression. The patient was hospitalized due to bulimia nervosa and mood disorders with suicidal thoughts in 2018. She was suffering from obesity with metabolic syndrome features and hypertension. She was diagnosed with Turner syndrome and received hormone replacement therapy in 2011. The patient had osteosarcoma surgery in 2011, and the treatment was last up to April 2012.
For nine years, the woman has had an eating disorder (manifested by excessive appetite) and emotional disturbance and self-harm to the body.
For six years (since 2015), she has felt sadness, difficulty concentrating and attention, disturbances of circadian rhythms (insomnia shift to excessive sleepiness) and induced vomiting, purging and starving. At the hospitalization time, the body weight was 122 kg, and body mass index (BMI) was 47.66 kg/m2 indicating 3rd degree of obesity.
During the physical examination, the patient reported the presence of suicidal thoughts, felt fear and anxiety. She has 11 points in the Mini-Mental State Examination, which indicates high suicide risk. The blood pressure was 169/116 mm Hg (3rd degree of hypertension), heart rate was 101 beats/minute (mild tachycardia). Due to persistently high blood pressure values, captopril was used as an emergency, followed by ramipril, furosemide and amlodipine. The antidepressant treatment included sertraline and trazodone. Laboratory tests revealed high blood glucose, insulin, hepatic enzymes, and coexisted obesity and metabolic syndrome futures, so metformin and tymonacyk were included to the treatment. Patient had vitamin D deficiency, and supplementation was started. The patient also received ethinyloestradiol with levonorgestrel. She received a proposition of realizing nutrition protocol KD. In addition to reducing body weight and improving biochemical parameters, KD would enhance the effectiveness of antidepressants.
To assess the effect of dietary intervention, structured scales and questionnaires were used: the Body Image Questionnaire (KWCO), Scale of satisfaction with parts and parameters of the body, The Scale for the Using of Methods for Correcting Appearance, Scale of Perception of Peer Messages, Scale of Self Constructs and Beck Depression Inventory Scale (BDI). The patient had critical thoughts towards her body and was not entirely sure of diet changes or physical activity, reducing body weight and improving her appearance. On the BDI scale, she received 40 points, which indicate severe depression.
The patient had the willingness and consent to attend to psychotherapy and psychoeducation and implement the dietary intervention. During the hospitalization, she had unstable and lower mood with periods of emotional irritability, tearfulness, increased severity of anxiety and sleep disturbances.
The patient had autoagressive thoughts without the tendency to realize them and had problems adapting to hospital rules.
At the starting point of the diet, her weight was 113.5 kg. The KD based on VLCKD protocol with four meals per day for four weeks was implemented. During the realization nutrition scheme, Kalibra medical protocol was used. The method had been developed in the United States 30 years ago. It included ready-to-eat food products and combining them with an unlimited amount of low-starch vegetables and nutrition supplements. It is necessary to enrich the diet of nutrients due to its low energy value. In Figure 1, an example of a one-day diet plan was shown.
During the therapy, the patient did not report dietrelated health problems. The body mass was reduced from 113.5 kg to 102 kg, and BMI was 39.9 kg/m2, indicating 2nd degree of obesity after the followed diet for four weeks. Despite a high reduction of body weight, the patient was not always willing to cooperate and to follow dietary recommendations. Her motivation had been fluctuated. She was still not satisfied with her appearance.
An improvement in well-being was achieved, the patient's mood was stabilized, the sense of anxiety decreased, and the circadian rhythm was normalized. She also denied the presence of suicidal thoughts. She received 23 points on the BDI scale, indicating moderate depression.
After the intervention, the weight has not been reducing. The diet with a limited amount of simple carbohydrates (so-called "diabetic diet") was recommended during later hospitalization time. At discharge, body weight was 102.7 kg (BMI 40 kg/ m2), which indicates 3rd degree of obesity. In the continuation of dietary recommendations, systematic consultations were recommended. The patient received an example of a 1-week dietary plan (1500 kcal per day) and general nutritional guidelines/suggestions. She declared willingness to therapy continuation. Below anthropometric measurements and laboratory test results of the patient during hospitalization was depicted.

Discussion
The presented study case indicates the potential efficacy of KD protocol as a co-therapy of obesity and mood disorder. The patient gradually gets physical and mental health improvement via psychological, pharmacological and dietary intervention during hospitalization.
Her mood stabilizes, the circadian rhythm has been regulated, depression symptoms occur less severe, and body weight was reduced by 20 kg. Following the KD has a positive effect on obesity treatment and improved some of the metabolic syndrome components. The patient did not report headaches, dizziness, fatigue, insomnia, decreased effort tolerance, constipation, nausea, and vomiting. These symptoms are described as a "keto flu" and occur in the implementing, adaptive organism phase for new metabolic conditions, f.e. elevated ketones concentration in blood serum and shift in using the primary energy sources substrates of body. The symptoms go away on their own from few days to weeks [12,15,17,18,19]. The quality of life and mood has also been improved, which was indicated by less severity of subjective symptoms. The results of intervention studies with individuals with depression indicate a decrease in body weight is accompanied by mood changes [20,21,22].
In a randomized clinical trial, SMILE following the nutrition protocol based on the Meditariean diet was an effective tool in an increase of potent therapy and the decrease mood symptoms [23]. In obese individuals (BMI upon 35 kg/m2), KD led to reduced body weight, glucose, LDL cholesterol, triglycerides blood concentration, and increased HDL cholesterol concentration [24]. As in our patient, after KD implementation, body weight was decreased, LDL, HDL and total cholesterol concentrations were reduced. The triglycerides level increased and fasting glucose was still maintained above 99 mg/dl. It was unclear wheather in described case, the relationship between KD and reduction of depressive symptoms is causality.
During following nutrition protocol, the patient received antidepressant medication and had psychotherapy and psychoeducation. It is worth mentioning that she could not determine the cause of her mood and behaviour during psychotherapy and moderate depressive symptoms maintained during discharge from the hospital. The nutrition and therapeutic cooperation  with her was difficult. She did not fully follow dietary recommendations. The patient was not interested in physical activity, and attempts to prompt for physical effort were ineffective.

Conclusions
The KD was added to pharmacological and psychological therapy for patient's treatment due to high BMI and her health risk. After the dietary intervention, the body weight was reduced, the metabolic parameters improved. The patient had partial remission of depressive symptoms after followed drug treatment and dietary protocol. In the described study case, the KD is an efficacy as a tool for treatment of obesity. However, determination of the antidepressant potent of protocol is impossible due to using numerous methods of mood disorders treatment simultaneously and lack of patient's cooperation.