|Year : 2021 | Volume
| Issue : 3 | Page : 80-85
Low-carbohydrate diet improves the cardiopsychiatry profile of patients with schizophrenia: A pilot study
Noor J Altooq1, Safa Abduljalil Aburowais1, Ahmed N Alajaimi1, Isa Y Albanna2, Omar A Alhaj3, Haitham A Jahrami4
1 Department of Psychiatry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
2 I.M. Sechenov First Moscow State Medical University, Moscow, Russia
3 Department of Nutrition, Faculty of Pharmacy and Medical Science, University of Petra, Amman, Jordan
4 Department of Psychiatry, College of Medicine and Medical Sciences, Arabian Gulf University; Psychiatric Hospital, Ministry of Health, Manama, Bahrain
|Date of Submission||24-Mar-2021|
|Date of Acceptance||10-Aug-2021|
|Date of Web Publication||29-Sep-2021|
Dr. Haitham A Jahrami
Ministry of Health, Manama, Bahrain, College of Medicine and Medical Sciences, Arabian Gulf University, 26671 P. O. Box: Manama
Source of Support: None, Conflict of Interest: None
Background and Objective: Patients with schizophrenia are more prone to develop metabolic syndrome (MetS) with its related complications, including cardiovascular diseases and diabetes mellitus compared to the general population. In this study, we aim to evaluate the effect of low-carbohydrate diet on MetS Z score, weight status, and symptomatology of patients with schizophrenia in Bahrain. Materials and Methods: This single-group pretest–posttest study was executed while considering an ethical approach of volunteer participants, a sample size of 35 patients with schizophrenia. The participants were instructed to follow a low-carbohydrate moderate-fat diet for 8 weeks. Anthropometric measurements, mean arterial pressure, basal metabolic index, body fat percentage (BFP), body surface area (BSA), and MetS Z score and Clinical Global Impression (CGI) Scale were collected before and after the diet intervention. Descriptive statistics, including the mean and standard deviations, were used for continuous variables and percentages for the categorical variables. Paired t-tests and effect size were used to analyze the mean difference of the values before and after the diet intervention. Results: A statistical significance in the mean difference was observed among the following variables: MetS Z score, weight, body mass index (BMI), high-density lipoproteins (HDL), low-density lipoprotein (LDL), thrombin generation test, waist circumference (WC), BFP, BSA, and CGI-improvement (CGI-I). Weight, BMI, TG, BFP, BSA, and CGI-I had a large effect size of the mean difference, whereas LDL, HDL, and WC had a moderate effect size. There was no statistically significant difference in the MetS Z score between male and female after the diet intervention (P = 0.274). Conclusion: Dietary modification with low-carbohydrates restriction is a workable approach in the management of schizophrenia and its related metabolic complications. Clinical trials need to be conducted to corroborate the implementation of dietary intervention as a co-treatment of schizophrenia.
Keywords: Low-carbohydrate diet, metabolic syndrome, Mets Z score, schizophrenia
|How to cite this article:|
Altooq NJ, Aburowais SA, Alajaimi AN, Albanna IY, Alhaj OA, Jahrami HA. Low-carbohydrate diet improves the cardiopsychiatry profile of patients with schizophrenia: A pilot study. Heart Mind 2021;5:80-5
|How to cite this URL:|
Altooq NJ, Aburowais SA, Alajaimi AN, Albanna IY, Alhaj OA, Jahrami HA. Low-carbohydrate diet improves the cardiopsychiatry profile of patients with schizophrenia: A pilot study. Heart Mind [serial online] 2021 [cited 2022 Nov 27];5:80-5. Available from: http://www.heartmindjournal.org/text.asp?2021/5/3/80/326962
| Introduction|| |
Alarming levels of premature mortality among individuals with schizophrenia are attributed to the high prevalence of metabolic syndrome (MetS).,, MetS is defined by the co-occurrence of insulin resistance, obesity, endothelial dysfunction, and dyslipidemia. Various low-carbohydrate diets, including ketogenic diet (KD), have been shown to improve the symptomatology of schizophrenia and reduce the impact of weight gain and metabolic dysfunction partly induced by antipsychotic medications. The research hypothesis postulates that a low-carbohydrate diet would have a positive impact on the management of schizophrenia. The current study aims to evaluate the effect of a low-carbohydrate diet on MetS Z score, weight status, and Clinical Global Impression (CGI) Scale of patients with schizophrenia in Bahrain.
| Materials and Methods|| |
In this single-group pretest–posttest study, data were collected between September and November 2019. Ethical approval was obtained from the Secondary Health Research Ethics Committee, Ministry of Health, Kingdom of Bahrain.
Participation in the study was voluntary and informed written consent was obtained from participants before data collection. Participation halted during Ramadan month to eliminate the metabolic influence of fasting on the components of MetS.
Participants and sample size
Participants in the study were registered at the Psychiatric Hospital (Outpatient Department), Ministry of Health in Bahrain. The Psychiatric Hospital is the main governmental center for the diagnosis and management of psychiatric illnesses in Bahrain. Patients were followed regularly with a visit once a month.
Patients with any type of schizophrenia who fit the diagnostic criteria of the International Classification of Disease 10th Revision, aged between 20 and 60 years, were included in the study.
Patients diagnosed with multiple psychiatric illnesses, pregnant and lactating women, patients undergoing different lifestyle modifications, and those enrolled in randomized control trials were excluded from the study.
The sample size was determined using the data of the National Noncommunicable Diseases Survey. Sample size calculation for the case–control design suggested a minimum of 30 subjects per group for viable analysis using an α (type I error) of 0.05 and β of 0.2 (type II error) assuming a paired sample difference of approximately 1.0 kg (effect size of 0.2) at the power of 80%.
Low-carbohydrate moderate-fat diet program
The recommended daily intake of carbohydrates is set at 45%–65% of total calories for healthy individuals. Due to the difficulty for the participants to strictly follow the KD (daily nutritional intake of 5–10% of carbohydrates) for 8 weeks besides that it results in inadequate insulin levels, they were instructed to follow a weekly program of low-carbohydrate moderate-fat diet for 8 weeks. Low-carbohydrate moderate-fat diet comprises 20% carbohydrates, 40% proteins, and 40% fat. This diet was previously reported in the management of type 1 diabetes and body fat loss. This diet offers a daily nutritional intake of 20% of carbohydrates equal to 100 g/d for 2000 kcal intake diet which is higher than the level of ketones produced in the urine for most persons. The participants had a weekly follow-up with a nutritional therapist to check their level of adherence to the diet and respond to their queries. The follow-up included revision of macro- and micronutrients intakes of food.
Assessments and data collection
Anthropometric measurements, blood pressure (BP), and biochemical analysis were collected from the participants. Mean arterial pressure (MAP), basal metabolic index, body fat percentage (BFP), body surface area (BSA), and MetS Z score were calculated using the collected data. Data collection and measurements were all conducted before and after the completion of 8 weeks of the low-carbohydrate moderate-fat diet program. Anthropometric measurements include weight, height, waist circumference (WC), and hip circumference (HC). Participants were instructed to wear light clothes, stand upright barefoot for optimal accuracy of the measurement. The technique of weight and height measurement was conducted using digital scales with height rod attachment that was placed on a hard, straight floor. Weight and height were approximated to the nearest 0.1 kg and 1 cm, respectively. All readings of anthropometric measurements were taken once before and after the intervention. Self-reported weight and height for body mass index (BMI) were valid for both sexes., BMI was calculated by dividing the weight (kg) over the square of height (m2). A standard body tape measure was used for the measurement of WC and HC. Participants were instructed to stand upright and values were approximated to the nearest 0.1 cm. To avoid any measurement errors, anthropometric measurements were all conducted by the same data collector who was blind from the purpose of the research.
The measurement of BP was done twice using the digital sphygmomanometer while the participant was in a sitting position. The participant had to rest for 10 min before taking the measurement. The average of both readings was calculated seeking more accuracy of the BP values.
MAP was calculated using a formula in which the diastolic BP (DBP) is doubled then added to the systolic BP (SBP) and that combined sum then is divided by three.
Fasting blood glucose
Participants were instructed to fast for 12 h before taking the blood sample. The analysis of the biochemical markers was held in an independent laboratory of the Department of Pathology at the Ministry of Health in Bahrain.
From the Bahraini electronic health records, medical data about the patient's prescriptions for abnormalities in their metabolic profile or their management were gathered.
Body fat percentage
BFP is a measure of adiposity; it is the proportion of body fat from the total body weight. BMI was used to estimate the BFP through a gender-specific formula. For an adult male, BFP = (1.20 × BMI) + (0.23 × Age) −16.2 and for an adult female, BFP = 1.20 × BMI + (0.23 × Age) −5.4.
Body surface area
BSA, a highly accurate estimation of metabolic mass, was calculated using the Mosteller formula
BSA (m2) = square root of (height [cm] × weight [kg]/3600)
MetS, as defined by International Diabetes Federation (IDF), is a combination of central body obesity determined a waist circumference ≥ of 94 cm for males and ≥80 cm for females (European values are used as a reference for Arab populations, Middle East Eastern and Mediterranean) along with two of the following factors:
- Hypertension (SBP ≥130 mmHg or diastolic blood ≥85 mm Hg), or on the treatment of previously diagnosed hypertension
- Fasting ≥blood glucose 5.6 mmol/L, or previously diagnosed with type II diabetes
- Blood triglycerides ≥1.7 mmol/L, or on specific treatment for dyslipidemia
- High-density lipoproteins (HDL) <1.03 mmol/L in male and <1.29 mmol/L in females or on specific treatment for dyslipidemia.
The metabolic syndrome Z score formula
The metabolic syndrome Z score formula, established by the (IDF-MetS score), was used to calculate the MetS Z score of the participants.
MetS Z score, a formula that uses the central components of MetS including waist circumference, systolic arterial pressure, triglycerides, HDL, and glucose for age and gender, assesses the severity of the MetS. A higher MetS Z score is associated with a higher risk of cardiovascular disease (CVD). The equation used was Z score = ([(1.03–HDL)/0.72] + [(TG–1.7)/0.51] + [(FBG–5.6)/1.1] + [(WC–94)/10.56] + [(MAP–95)/10.9]).
Clinical Global Impression Scale
CGI was used to assess the improvement and the severity of schizophrenia across time. CGI measures the difference in both variables using the patient's history, psychological symptoms, and information given from the patient's community, such as family members before and after a certain clinical intervention. CGI-improvement (CGI-I) and CGI-severity (CGI-S) are scaled from 1 to 7 based on the clinician's point of view. On the CGI-I scoring scale, the score 1 stands for very much improved and the score 7 for much worst. In the CGI-S, the score of 1 means normal, while the score of 7 shows that the person is severely impaired. Any changes in the CGI-I score are not going to affect the CGI-S score and vice versa.
A correlation exists between CGI scale and PANSS in which both measures show consistency in tracking therapeutic response or progression of the disease over time. CGI criterion offers a quantification tool for treatment and a valid and easy alternative for daily clinical practice.,
Descriptive statistics were used to present the demographic characteristics of the participants, the values of MetS components, MetS Z score, BSA, BFP, and CGI scale. The means and standard deviations (SD) were used for continuous variables and percentages for the categorical variables. Paired t-tests were used to analyze the mean difference of the values before and after the low-carbohydrate diet intervention. Cohen's d was calculated to find the effect size of the variables. ANCOVA was used to test for statistical significance in the MetS Z score of males and females. Schefft's test was performed to determine the major factors affecting the value MetS Z score. Significance was set at the level of 5%. The statistical analysis was performed using IBM SPSS Inc. Software version 26, Chicago, Illinois, USA.
| Results|| |
A total of 35 patients with schizophrenia, including 25 males (71.43%) and 10 females (28.57%), were recruited to take part in the study. Descriptive statistics of the participants before and after the low-carbohydrate diet intervention are shown in [Table 1].
|Table 1: Demographic characteristics of the participants before and after low-carbohydrate diet intervention|
Click here to view
Metabolic syndrome Z score
The 35 participants had a mean difference from preintervention to postintervention of MetS Z score of 0.324 (SD = 0.886), showing that the intervention of 8 weeks of low-carbohydrate diet resulted in a significant decrease in the MetS Z score (P = 0.038) with a moderate effect size according to Cohen's d (effect size of 0.365) [Table 2]. Based on the ANCOVA test, there was no statistically significant difference in the MetS Z score between males and females after the diet intervention (P = 0.274) [Table 3]. Scheffe's test has shown that WC and MAP of the participants were the two major components affecting the changes in the value of MetS Z score after the dietary intervention.
|Table 2: Mean differences of the parameters before and after the low-carbohydrate diet intervention|
Click here to view
|Table 3: Gender difference in the metabolic syndrome Z score (dependent variable)|
Click here to view
Weight status and metabolic syndrome components
Significance in the mean difference was observed among the following variables: weight (P < 0.001), BMI (P < 0.001), HDL (P < 0.001), low-density lipoprotein (LDL) (P < 0.001), thrombin generation test (P < 0.001), waist circumference (P < 0.001), BFP (P < 0.001), and BSA (P < 0.001) showing a significant preference for the intervention of 8 weeks of low-carbohydrate diet on the values. However, there was not any significance noted in the mean difference of SBP, DBP, MAP, and fasting blood glucose (FBG) [Table 2]. Weight, BMI, TG, BFP, and BSA had a large effect size of the mean difference, whereas LDL, HDL, and WC had a moderate size effect according to Cohen's d [Table 2].
Psychiatric symptomatology (Clinical Global impression Scale)
CGI-I had shown to have a significant mean difference with a large effect size (effect size of − 0.945) (P < 0.001), showing that the intervention of 8 weeks of low-carbohydrate diet resulted in a significant improvement in the CGI-I scale. However, CGI-S showed no difference in the mean before and after the low-carbohydrate diet intervention [Table 2].
| Discussion|| |
Patients with schizophrenia are more inclined to have a high cardiometabolic risk because of its association with MetS. This extremely strengthens the notion that patients with schizophrenia need to be strictly followed and managed for the metabolic sequelae of the pathophysiology of the disorder and side effects of antipsychotic medications.
The main aim of the study is to assess the effect of low-carbohydrate diet on MetS Z score, weight status, and symptomatology of patients with schizophrenia and evaluate its feasibility as an additional therapeutic approach in the management of schizophrenia.
Bodyweight, BMI, LDL, BFP, and BSA all significantly reduced after the low-carbohydrate diet intervention. This is consistent with the outcomes observed in KD intervention used for patients with schizophrenia concerning the decrease in body fat and weight status., A study emphasizes that patients with schizophrenia have a five times higher risk of gaining visceral fat compared to normal healthy individuals, which increases the cardiovascular risk. Diet intervention combined with lifestyle modification was a quite effective and safe approach in the management of weight gain induced by antipsychotic medications based on a systematic review.
The significant level of reduction in some of the MetS components, including WC, HDL, and TG, was further noted for both genders. MetS Z score has shown a significant improvement after the applied dietary program. In this context, the major factor affecting and mediating the improvement in MetS Z score appeared to be the WC. This result points us toward the probability that a correlation between the WC and the risk of cardiovascular outcome could exist, linked by its association with MetS Z score. Similar to a study conducted on prediabetes patients, lifestyle modifications and prediabetes treatment resulted in an improvement in MetS Z score and proved its association with the risk of developing CVD and type 2 diabetes mellitus. Notably, low-carbohydrate diet has been shown to have a major role in stabilizing blood glucose and insulin levels, which positively reflects on the overall risk of diabetes mellitus. This suggests that a low-carbohydrate moderate-fat diet followed for 8 weeks would improve the status of MetS. Following the diet for more time may drastically improve the results as well.
CGI-S scale of the participants remained stable throughout the study, which might be accounted for the short period of the dietary intervention. The CGI-I scale showed a significant improvement after the completion of 8 weeks of the low-carbohydrate diet. A case report study presenting a 70-year-old Caucasian woman with schizophrenia showed an obvious improvement of hallucinatory symptoms just after consuming a restricted carb diet which allowed <20 g of daily carb intake for 7 days with no recurrence of psychiatric symptoms.
A low-carbohydrate diet has been widely used to treat epilepsy in children.,, The mechanism of action of antiepileptic medications relies partly on increasing the synaptic levels of gamma-aminobutyric acid (GABA). In the same context, it has been proven that patients with schizophrenia have a disruption in the GABA: glutamate ratio besides abnormal glucose metabolism and mitochondrial dysfunction which alter the normal communication of synapses in the brain. It has been hypothesized that the KD plays a major role in restraining the catabolism of GABA,, which is similar to the action of antiepileptic medications. This collectively provides a sign that a low-carbohydrate diet can contribute to the stabilization and amelioration of psychiatric symptomatology of patients with schizophrenia by minimizing the biochemical disturbance in their brain.
Since KD is potentially difficult with patients with neuropsychiatric diseases such as schizophrenia and because of its extreme restriction of carbohydrates intake, a “low-carbohydrate diet” which offers a daily nutritional intake of 20% of carbohydrates might serve as a flexible alternative to patients with schizophrenia to maintain a higher level of adherence and improve their metabolic profile and symptoms. We acknowledge that a low-carbohydrate diet can be expensive for patients; however, low-carbohydrate diet may offer a cost-effective approach in the management of schizophrenia compared with medical costs. In this regard, the KD has shown to provide financial support and reduction of medical costs if successfully maintained by children with intractable epilepsy. It is worth noting that adherence to low-carbohydrate moderate-fat diet may place an economic burden on patients living in low-income countries.
The accuracy of this study could be improved if it was conducted on inpatient participants rather than outpatients for better standardization of the quantity and quality of the diet. Monitoring the compliance of the participants would reveal more details on the stages of weight loss experienced during the study. This warrants a higher level of control and frequent follow-up measurement of the weight to be considered in future studies to recognize the pattern of weight change throughout the full period of dietary intervention. The small number of patients with schizophrenia in Bahrain and the short period of the intervention have further limited the study. The small sample size may have resulted in the emergence of accidental statistical significance in the mean difference of the studied variables. Besides, BFP was indirectly measured depending on the values of BMI which is not an accurate indicator of body fat. BMI overestimates body fat in individuals with high muscle mass and bone density. The effectiveness of the intervention could be better assessed by conducting a randomized control trial study that provides a comparison with the metabolic profile and psychiatric symptomatology of patients with schizophrenia not following any dietary regimen.
| Conclusion|| |
Dietary modification such as low-carbohydrate restriction is a workable approach in the management of schizophrenia and its related metabolic complications. Further large-sized randomized clinical trials need to be conducted to confirm the findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Correll CU, Detraux J, De Lepeleire J, De Hert M. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015;14:119-36.
Malhotra N, Grover S, Chakrabarti S, Kulhara P. Metabolic syndrome in schizophrenia. Indian J Psychol Med 2013;35:227-40.
] [Full text]
Chadda RK, Ramshankar P, Deb KS, Sood M. Metabolic syndrome in schizophrenia: Differences between antipsychotic-naïve and treated patients. J Pharmacol Pharmacother 2013;4:176-86.
] [Full text]
Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009;2:231-7.
Gilbert-Jaramillo J, Vargas-Pico D, Espinosa-Mendoza T, Falk S, Llanos-Fernandez K, Guerrero-Haro J, et al
. The effects of the ketogenic diet on psychiatric symptomatology, weight and metabolic dysfunction in schizophrenia patients. Clin Nutr Metab 2018;1:1-5.
Seckold R, Fisher E, de Bock M, King BR, Smart CE. The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: A review of clinical outcomes. Diabet Med 2019;36:326-34.
Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, et al.
Calorie for calorie, dietary fat restriction results in more body fat loss than carbohydrate restriction in people with obesity. Cell Metab 2015;22:427-36.
Westman EC, Feinman RD, Mavropoulos JC, Vernon MC, Volek JS, Wortman JA, et al
. Low-carbohydrate nutrition and metabolism. Am J Clin Nutr 2007;86:276-84.
Hodge JM, Shah R, McCullough ML, Gapstur SM, Patel AV. Validation of self-reported height and weight in a large, nationwide cohort of U.S. adults. PLoS One 2020;15:e0231229.
Davies A, Wellard-Cole L, Rangan A, Allman-Farinelli M. Validity of self-reported weight and height for BMI classification: A cross-sectional study among young adults. Nutrition 2020;71:110622.
Nieman DC, Carlson KA, Brandstater ME, Naegele RT, Blankenship JW. Running endurance in 27-h-fasted humans. J Appl Physiol 1987;63:2502-9.
Lee A, Gurka M, DeBoer M. Correlation of metabolic syndrome severity with cardiovascular health markers in adolescents. Metabolism 2017;69:87-95.
Rabinowitz J, Mehnert A, Eerdekens M. To what extent do the PANSS and CGI-S overlap? J Clin Psychopharmacol 2006;26:303-7.
Busner J, Targum SD. The clinical global impressions scale: Applying a research tool in clinical practice. Psychiatry (Edgmont) 2007;4:28-37.
Pinna F, Deriu L, Diana E, Perra V, Randaccio R, Sanna L, et al
. Clinical Global impression-severity score as a reliable measure for routine evaluation of remission in schizophrenia and schizoaffective disorders. Ann Gen Psychiatry 2015;14:6.
Taus M, Fumelli D, Busni D, Borroni F, Sebastianelli S, Nicolai G, Nicolai A. A very low calorie ketogenic diet improves weight loss and quality of life in patients with adjustable gastric banding. Ann Ital Chir. 2017;88:143-8.
Konarzewska B, Stefańska E, Wendołowicz A, Cwalina U, Golonko A, Małus A, et al
. Visceral obesity in normal-weight patients suffering from chronic schizophrenia. BMC Psychiatry 2014;14:35.
Gurusamy J, Gandhi S, Damodharan D, Ganesan V, Palaniappan M. Exercise, diet and educational interventions for metabolic syndrome in persons with schizophrenia: A systematic review. Asian J Psychiatry 2018;36:73-85.
DeBoer MD, Filipp SL, Gurka MJ. Use of a metabolic syndrome severity Z
score to track risk during treatment of prediabetes: An analysis of the diabetes prevention program. Diabetes Care 2018;41:2421-30.
Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: A case report and review of the literature. Nutr Metab (Lond) 2009;6:10.
Sampaio LP. Ketogenic diet for epilepsy treatment. Arq Neuropsiquiatr 2016;74:842-8.
Bostock EC, Kirkby KC, Taylor BV. The current status of the ketogenic diet in psychiatry. Front Psychiatry 2017;8:43.
Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012;3:59.
Bough K, Rho J. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 2007;48:43-58.
Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: Clinical implication. Curr Opin Psychiatry 2019;32:394-401.
Masood W, Annamaraju P, Uppaluri KR. Ketogenic diet. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2021.
Włodarczyk A, Wiglusz MS, Cubała WJ. Ketogenic diet for schizophrenia: Nutritional approach to antipsychotic treatment. Med Hypotheses 2018;118:74-7.
Mandel A, Ballew M, Eric Pina-Garza J, Stalmasek V, Clemens L. Medical costs are reduced when children with intractable epilepsy are successfully treated with the ketogenic diet. J Am Diet Assoc 2002;102:396-8.
[Table 1], [Table 2], [Table 3]