The Evaluation of the Efficacy of a Fasting Mimicking Diet Added to Functional Therapy for Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      Depression has to be considered as a systematic illness involving the whole body, it is often
      associated with low-grade inflammation and alterations of the microbiome. In this regard, an
      unhealthy diet increases the risk of the onset of this disorder, therefore an integrated
      treatment including a healthy diet could be more effective. The aim of our study were to
      verify the efficacy of a structured FT program, delivered in individual setting, for patients
      with depression (PSY group), and to verify whether the association of a FMD protocol with the
      structured FT program significantly improves clinical outcomes (PSY-FMD group). After a
      psychiatric, psychological and anthropometric assessment, depressed patients were randomly
      assigned to psychotherapy and diet (PSY-FMD) or just psychotherapy (PSY). PSY-FMD
      participants received 20 individual sessions of Functional Psychotherapy. Each session
      attended twice a week for the first 8 weeks and once a week for the remaining 4. Furthermore,
      they received a nutritional consultation and prescription of a Fasting Mimicking Diet. PSY
      group received just the psychotherapy protocol and the nutritional consultation. All patients
      were retested at the end of the treatment and at follow-up 3 months after the last session.
      In both groups was highlighted a strong effectiveness of treatments on depression,
      self-esteem and quality of life. In the PSY-FMD group compared to PSY a significant effect
      was found on the improvement of self-esteem and quality of life. Furthermore, a significant
      reduction of BMI was found in the PSY-FMD group. The current study supports the effectiveness
      of the combination of psychotherapy with a fasting mimicking diet in adult depressed
      patients.
    

Detailed description: 
      Depression is considered as a systemic illness affecting the whole body and increasing the
      risk of several diseases. Several studies showed an important link between depression and
      inflammation. Indeed, depression is associated with the activation of peripheral and central
      immune-inflammatory pathways indicated by increased levels of proinflammatory cytokines, such
      as Interleukin-1 β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNFα) and
      Interferon-γ (IFNγ). Furthermore, depressed patients present high levels of C-reactive
      Protein (CRP).

      Furthermore, several studies underlined the existence of a link between depression and
      alterations of the microbiome, as the gut microbiota is implicated as an important health
      determinant relevant to mental health Several psychotherapy programs have demonstrated to be
      effective in treating depression, such as Cognitive-Behavioral Therapy (CBT), psychodynamic
      approaches and mind-body approaches, such as yoga and meditation.

      There is some empirical evidence suggesting that the Functional Therapy (FT) approach, that
      represents an integrated body-mind therapy, highlights the possibility of inducing real
      changes of the cognitive, emotional and psychological systems through direct body
      intervention. The purpose of FT for depression is to increase mood and self-esteem through
      several bodily, cognitive, and emotional techniques by helping depressed patients to improve
      the Basic Experiences of the Self (BES) altered in this disorder. Furthermore, the integrated
      treatment provides an overall framework to facilitate lifestyle changes reinforcing
      assertiveness and self-efficacy.

      A considerable body of literature highlighted the role of a healthy diet for reducing the
      risk of depression. On the other side, a diet based on Western dietary pattern is associated
      with depressed mood and anxiety. The typology of diet also modulates several key biological
      processes that underscore mood disorders, such as brain plasticity, stress response system,
      inflammation, and oxidative processes. Furthermore, practicing a Western dietary pattern
      implicates a negative effect on our immune system, associating with higher inflammation, and
      food-related inflammation is associated to increased risk of depression. Indeed, high stress
      levels and poor diet may lead to a disruption of the Hypothalamic-Pituitary-Adrenal (HPA)
      axis, with consequent increasing of cortisol's level, low-grade systemic inflammation and
      oxidative stress.

      In this regard, a specific typology of diet oriented on fasting has proved to be effective on
      several parameters related to health. Cheng and colleagues (2014) found that periodic
      prolonged fasting promote stress resistance, self-renewal, and lineage-balanced regeneration;
      moreover, their results showed that cycles of fasting reduced the immunosuppression and
      mortality caused by chemotherapy in mice. A gradual calorie restriction, mimicking fasting
      effects but providing all macro- and micro-nutrients on mice rejuvenated the immune system,
      extended longevity, bring to lowered visceral fat, reduced cancer incidence and retarded bone
      mineral density loss. Furthermore, the authors found that in old mice FMD cycles promoted
      hippocampal neurogenesis and improved cognitive performance and motor coordination. Moreover,
      a Fasting Mimicking Diet protocol was associated with a significant reduction of TNFα, IL-1β
      and IL-6, and this decrease could positively influence the mood.

      Given these premises, the aim of this clinical trial were:

        1. Verify the efficacy of a structured FT program, delivered in individual setting, for
           patients with depression (PSY group);

        2. Verify whether the association of a FMD protocol with the structured FT program
           significantly improves clinical outcomes (PSY-FMD group).

      Patients were enrolled from January 2018 to March 2019 and were recruited via advertisement
      posted in our outpatient clinic. For the recruitment a structured telephone screening helped
      the researchers to investigate on some exclusion criteria. Then a consultation with a
      clinical psychologist and with a psychiatrist were programmed together with the
      administration of the psychological tests. Psychological assessment included an ad-hoc
      sociodemographic questionnaire; a shortened version of Wechsler Adult Intelligence Scale -
      Revised (WAIS-R); Millon Clinical Multiaxial Inventory-III (MCMI-III); Beck Depression
      Inventory-II (BDI-II); Basic Self-Esteem Scale (Basic SE); World Health Organization Quality
      of Life-BREF (WHOQOL-BREF). Anthropometric parameters included weight, height and waist
      circumference.

      Six different therapists with a 4-year postgraduate training on FT applied the intervention.
      All therapists took part to a refresher training oriented to the application of the
      structured FT protocol for depression. Each therapist treated four patients. A nutritionist
      prescribed the FMD protocol after a consultation. After the assessment, eligible subjects
      were randomized in the PSY-FMD group or in the PSY group and were assigned to the next
      therapist on a time capacity list. A block randomization was used, so that number of patients
      per condition were balanced within therapists. The resulting samples comprised 20 depressed
      subjects. Four patients dropped out. There were no pre-treatment group differences on age,
      sex, marital status and years of education. Furthermore, both groups were homogeneous on
      Intelligence Quotient, the presence of psychiatric comorbidities or personality disorders, as
      well as for the level of depression, self-esteem, quality of life and BMI.

      Ten subjects were randomized in the PSY-FMD group and they carried out the FT protocol over
      20 individual sessions, which were scheduled twice a week for the first two months and once a
      week for the last month (three months total). None of the patients were undergoing
      psychopharmacological treatment. The treatment program was specifically manualized for
      treating depression with the aim to increase mood, self-esteem and quality of life.
      Specifically, the treatment program was oriented towards the reduction and/or elimination of
      mood unbalance through several bodily, cognitive and emotional techniques, such as deep
      breathing, specific guided imagery, techniques for improving assertiveness and for improving
      social abilities. Furthermore, patients recruited in the PSY-FMD group, followed a FMD
      protocol consisting of 3 cycles of 5 days a month each: the first day of the diet provided
      1090 kcal (10% protein, 56% fat, 34% carbohydrate), the days 2-5 were identical in the
      formulation and provided 725 kcal (9-10% protein, 44-56% fat, 34-47% carbohydrate). Between
      cycles of FMD the subjects stuck to a free diet.

      Ten subjects were randomized into the control group (PSY) and completed the same FT program
      without practicing any diet. Specifically, at the end of the nutritional consultation the
      nutritionist suggested them to keep a food diary without changing their habitual diet style.

      At the end of the treatment all patients were re-tested through the same assessment protocol
      (psychological tests, anthropometric measures and nutritional consultation) to analyse the
      achievement of the expected outcomes and the same things was realized at the follow-up (three
      months later the end of the treatment).

      Group differences in demographic features and pre-treatment measures were analysed with
      independent samples t-tests and χ2- tests. In order to evaluate the pre-post treatment
      alterations, a repeated ANOVA measurement was used at baseline, at the end of treatment and
      at the follow-up period. All analyses assumed an alpha risk of 5%. All statistical analyses
      were conducted using Statistical Package for Social Science for Windows 22.0.
    

Intervention name(s): Fasting Mimicking Diet
Intervention type(s): Dietary Supplement
Intervention description(s): The Fasting Mimicking Diet is a low-calorie, five-day eating program meant to promote weight loss and provide the same benefits as more traditional fasting methods.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: After a psychiatric, psychological and anthropometric assessment, depressed patients were randomly assigned to psychotherapy and diet (PSY-FMD) or only psychotherapy (PSY) groups. PSY-FMD participants received 20 individual sessions of Functional Psychotherapy. Each session attended twice a week for the first 8 weeks and once a week for the remaining 4. Furthermore, they received a nutritional consultation and prescription of a Fasting Mimicking Diet. PSY group received just the psychotherapy protocol and the nutritionist prescribed to keep a food diary without changing their habitual diet style. All patients were retested at the end of the treatment (3 months later) and at follow-up 3 months after the last session.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Depression; Fasting Mimicking Diet; Functional Therapy; Lifestyle Medicine; Health Psychology; Psychosomatic